A Computational Predictor for Accurate Identification of Tumor Homing Peptides by Integrating Sequential and Deep BiLSTM Features.

Cancer remains a severe illness, and current research indicates that tumor homing peptides (THPs) play an important part in cancer therapy. The identification of THPs can provide crucial insights for drug-discovery and pharmaceutical industries as they allow for tailored medication delivery towards cancer cells. These peptides have a high affinity enabling particular receptors present upon tumor surfaces, allowing for the creation of precision medications that reduce off-target consequences and enhance cancer patient treatment results. Wet-lab techniques are considered essential tools for studying THPs; however, they're labor-extensive and time-consuming, therefore making prediction of THPs a challenging task for the researchers. Computational-techniques, on the other hand, are considered significant tools in identifying THPs according to the sequence data. Despite many strategies have been presented to predict new THP, there is still a need to develop a robust method with higher rates of success. In this paper, we developed a novel framework, THP-DF, for accurately identifying THPs on a large-scale. Firstly, the peptide sequences are encoded through various sequential features. Secondly, each feature is passed to BiLSTM and attention layers to extract simplified deep features. Finally, an ensemble-framework is formed via integrating sequential- and deep features which are fed to a support vector machine which with 10-fold cross-validation to carry to validate the efficiency. The experimental results showed that THP-DF worked better on both [Formula: see text] and [Formula: see text] datasets by achieving accuracy of > 95% which are higher than existing predictors both datasets. This indicates that the proposed predictor could be a beneficial tool to precisely and rapidly identify THPs and will contribute to the cutting-edge cancer treatment strategies and pharmaceuticals.

An explainable stacking-based approach for accelerating the prediction of antidiabetic peptides.

Diabetes is a chronic disease that is characterized by high blood sugar levels and can have several harmful outcomes. Hyperglycemia, which is defined by persistently elevated blood sugar, is one of the primary concerns. People can improve their overall well-being and get optimal health outcomes by prioritizing diabetes control. Although the use of experimental approaches in diabetes treatment is cost-effective, it necessitates the development of many strategies for evaluating the efficacy of therapies. Researchers can quickly create new strategies for managing diabetes and get vital insights by enabling virtual screening with computational tools and procedures. In this study, we suggest a predictor named STADIP (STacking-based predictor for AntiDiabetic Peptides), a new method to predict antidiabetic peptides (ADPs) utilizing a stacked-based ensemble approach. It uses 12 different feature encodings and seven machine-learning techniques to construct 84 baseline models. The impacts of various baseline models on ADP prediction were then thoroughly examined. A two-step feature selection method, eXtreme Gradient Boosting with Sequential Forward Selection (XGB-SFS), was employed to determine the optimal number, out of 84 PFs to enhance predictive performance. Subsequently, utilizing the meta-predictor approach, 45 selected PFs were integrated into an XGB classifier to formulate the final hybrid model. The proposed method demonstrated superior predictive capabilities compared to constituent baseline models, as evidenced by evaluations on both cross-validation and independent tests. During extensive independent testing, STADIP achieved promising performance with accuracy and mathew's correlation coefficient of 0.954 and 0.877, respectively. It is anticipated that it will be useful tool in helping the scientific community to identify new antidiabetic proteins.

Cockroaches as carriers of human medically important parasites.

Cockroaches have been identified as mechanical carriers of pathogens capable of infesting humans. The primary objective of this research was to detect and separate medically significant parasites found within the collected cockroaches. A total of 185 cockroaches were captured. In the laboratory, cockroaches underwent a series of steps. Initially, they were washed in a saturated salt solution and rinsed with 70% alcohol, dried, and subsequently dissected to examine endoparasites. In this study, a transport rate of 29.729% was documented, and four types of helminths were identified, which included Ascaris lumbricoides (47.27%), Enterobius vermicularis (30.91%), Trichuris spp. (7.27%), and Hymenolepis nana (14.55%). The parasites were more frequently found on the external surface of cockroaches (38/69.09%), compared to the internal surface (17/30.91%). Cockroaches captured in toilets were found to carry a higher percentage of parasites (31/16.75%) compared to those from kitchens (11/5.94%) and houses (13/7.02%). These findings suggest that cockroaches can serve as carriers for intestinal parasites and potentially act as mechanical agents in the dissemination of these parasites.

Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer.

BACKGROUND: FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. OBJECTIVE: The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. METHODS: This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs' associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. RESULTS: The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC's stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p, respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. CONCLUSIONS: The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC.

Targeting inflammation for the treatment of endometritis in bovines.

The uterine endometrial surface of bovines is in constant exposureconstantly exposed with to a multitude ofmany microbial populations that changes throughout the post-partum phase in terms of complexity and dynamics. These microbes contribute to the host pathology, leading to severe economic losses along withnd reproductive capabilities. The basic primary interface that occurs between the internal tissues of the body of the hostbetween the host body's internal tissues and the microbes is the endometrial surface of the uterus. As a result of the infinite pathogenic population, there is always a danger for the opportunistic organisms to attack. Therefore, it is paramount that any interactions, especially microbial microbes with the endometrial surface, are regulated by the host cells. However, the inflammatory response as the defense mechanism contributes a pivotal roleis pivotal in host immunity and pathology. The inflammatory cascade and pathways are important essential to eliminate this clinical problem. In this review, we will discuss and explain how the inflammation and the various components of the immune system play their role in host pathology and therapeutic strategies, taking into account the interface between the host and the microbes on the surface of the endometrium. This review is also instrumental in further explanation of inflammatory uterine disease by discussing the response of inflammation to external insult.

Intra-individual comparison of prostate-specific membrane antigen positron emission tomography/computed tomography versus bone scan in detecting skeletal metastasis at prostate cancer diagnosis.

OBJECTIVES: To compare the diagnostic performance and radiological staging impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to 99 Tc whole-body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa). PATIENTS AND METHODS: A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as 'negative', 'equivocal', or 'definite' based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases). RESULTS: There were 667 patients included. The median (interquartile range) prostate-specific antigen level was 9.2 (6.2-16) ng/mL and 60% of patients were high risk according to a modified D'Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high-risk (P = 0.030) and low-risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUVmax ) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUVmax of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high-risk patients. The SUVmax of the primary tumour and metastases was associated with upstaging.

Augmentation plate without bone graft in the management of distal tibial diaphyseal non-union.

PURPOSE: The objective of this study was to assess the efficacy of augmentation plating with retaining of previous implant in situ in cases of non-united oligotrophic or atrophic aseptic distal tibial diaphyseal and metaphyseal fractures without bone grafting depending on the unified bone healing and non-union theory. METHODS: Through the period between December 2019 and December 2022, twelve patients with distal third tibial non-unions who were fixed at time of fracture either by intramedullary interlocking nails (seven cases) or by minimally invasive plate osteosynthesis (five cases) were included. Non-union was diagnosed on basis of absence of any healing progression in three months period or absence of fracture healing after six months from index surgery. All patients had oligotrophic or atrophic non-union. Augmentation plating through an anterolateral approach was done on average of 7.25 months after initial surgery (6-9 months). Circumferential exposure of the fracture site and debridement of fibrous tissue were not necessary. No bone grafting was done as no cases had major bone defect. RESULTS: All patients achieved complete radiological union with a mean time of 21.8 weeks (range 18-30 weeks) that mean full callus formation in all cortices. All patients were walking independently after three months (13weeks) from surgery and returned to work even in cases of absent complete radiological union. No cases had been complicated with wound healing problems (infection or dehiscence). One patient had incomplete ankle dorsiflexion (10°) due to tight calf muscles and one patient had paresthesia on the dorsum of the foot that was not improved at last follow up (one year after surgery). CONCLUSION: Augmentation plating is a safe and effective option for management of distal tibial diaphyseal nonunion even in cases of oligotrophic or atrophic non-union.

Implementing failure mode and effect analysis to improve the safety of volumetric modulated arc therapy for total body irradiation.

PURPOSE: Volumetric-modulated arc therapy for total body irradiation (VMAT-TBI) is a novel radiotherapy technique that has been implemented at our institution. The purpose of this work is to investigate possible failure modes (FMs) in the treatment process and to develop a quality control (QC) program for VMAT-TBI following TG-100 guidelines. METHODS: We formed a multidisciplinary team to map out the complete treatment process of VMAT-TBI following the AAPM TG-100 guidelines. This process map gives a visual representation of the VMAT-TBI workflow from the CT simulation, image processing, contouring, treatment planning, to treatment delivery. From the process map, potential FMs were identified. The occurrence (O), detectability (D), and severity of impact (S) of each FM were assigned according to scoring criteria (1-10) by the multidisciplinary team. A risk priority number (RPN) was calculated from average O, S, and D of each FM (RPN = O x S x D). High risk FMs were identified as 20% of the FMs having the highest RPN scores. After the FMEA analysis, fault-tree analysis (FTA) was performed for each major step of the treatment process to determine the effects of potential failures to the treatment outcome. Effective QC methods were identified to prevent the high risk failures and to improve the safety of the VMAT-TBI program. RESULTS: We identified a total of 55 sub-processes and 128 FMs from the VMAT-TBI workflow. The top five high-risk FMs were: (1) Prescription and/or OAR constraints changed during planning and not communicated to the planner, (2) Patient moves or breathes too heavily during the upper body CT scan (3) Patient moves during the lower body CT scan, (4) Treatment planning system not calculating total body DVH metrics correctly for TBI, (5) Improper optimization criteria used or not sufficient optimization, resulting in suboptimal dose coverage, OAR sparing or excessive hotspots during treatment planning. Two FMs have average severity scores ≥8: Incorrect PTV subdivision/isocenter placement and Prescription and/or OAR constraints changed during planning and not communicated to the planner. Quality assurance and QC interventions including staff training, standard operating procedures, and quality checklists were implemented based on the FMEA and FTA. CONCLUSION: FM and effect analysis was performed to identify high-risk FMs of our VMAT-TBI program. FMEA and FTA were effective in identifying potential FMs and determining the best quality management (QM) measures to implement in the VMAT-TBI program.

Nutritional Assessment in Cancer Patients.

Malnutrition in cancer patients is highly prevalent. The metabolic and physiologic changes associated with the disease and the side effects of treatment regimens all combine together to produce a detrimental effect on the patient's nutritional status. A poor nutritional status significantly reduces the efficacy of treatment methods and the patient's overall chances of survival. Therefore, an individualized nutrition care plan is essential to counter malnutrition in cancer. Nutritional assessment is the first step of this process which sets the foundation for developing an effective intervention plan. Currently, there is no single standard method for nutritional assessment in cancer. Hence, to get a true picture of the patient's nutritional state, a comprehensive analysis of all aspects of the patient's nutritional status is the only reliable strategy. The assessment includes anthropometric measurements and evaluation of body protein status, body fat, inflammation markers, and immune markers. A thorough clinical examination which factors in the medical history and physical signs, along with the dietary intake patterns of the patient, is also important components of nutritional assessment of cancer patients. To facilitate with the process, various nutritional screening tools like patient-generated subjective global assessment (PGSGA), nutrition risk screening (NRS), and malnutrition screening tool (MST) have been developed. While these tools have their own benefits, they only give a glimpse of the nutritional problems and do not bypass the need for a complete assessment employing various methods. This chapter covers all four of the elements of nutritional assessment for cancer patients in detail.

Vaping and Mental Health Conditions in Children: An Umbrella Review.

The e-cigarette (EC) epidemic began in the United States (US) in 2007; since 2014 EC is the most commonly used form of tobacco. However, the mental health implications of vaping are grossly unknown. The aim of this umbrella review is to provide astate-of-the-art summary of existing research concerning vaping and mental health conditions in children. Following the PRISMA Statement 2020 guidelines, a systematic search was conducted across PubMed, Cochrane Library, and Google Scholar up to April 15th, 2022 to locate relevant studies. The Joana Briggs Institute (JBI) methodology for umbrella reviews and quality appraisal tool was utilized. Six studies, pooling a total of 846,510 adolescents aged 21 years or below, were included by collating 85 primary clinical studies. Of these, 58.8% of the primary clinical studies originated in the US, with 4.7% from Canada, South Korea, and the United Kingdom each; 3.5% each from England and Taiwan; 2.4% each from Australia, France, Hawaii, Mexico, and Russia; and 1.2% each from Denmark, Greece, Hong Kong, Iceland, New Zealand, Poland, and Switzerland. Overall, significant associations were found between mental health outcomes, including depression and suicidality, among current EC users and those who had ever used EC. Compared to adolescents who had never used EC, both depression and anxiety were reportedly higher among EC users. Impulsive behaviors, reported as impulsivity, were also found to be correlated with the adoption of EC use. However, there is a lack of evidence regarding the impact of EC use on mental health outcomes in children. This umbrella review highlights the urgent need to further explore the effects of current EC use from a psychiatric and public health perspective.

The risk of central nodal metastasis based on prognostic factors of the differentiated thyroid carcinoma: a systematic review and meta-analysis study.

BACKGROUND AND AIM: Despite improving the 10-year disease-free-survival, prophylactic central neck dissection (pCND) in differentiated thyroid carcinoma (DTC) should only be considered in patients with high risk factors for lymph node (LN) metastasis due to the increases in the risk of postoperative complications. Our aim was to identify the risk factors for central lymph node metastasis (CLNM) in DTC. METHOD: We searched PubMed, Scopus, Web of science, Cochrane library for eligible studies from inception to November 1, 2021 and a systematic review and meta-analysis were carried out to identify the risk factors for CLNM in DTC. RESULTS: We included 41 studies with total of 27,741 patients in this study. The pooled results in this meta-analysis showed that these risk factors were significantly associated with CLNM: age < 45 years (odds ratio (OR) 1.64, 95% confidence interval (CI) 1.34-1.99, p < 0.00001), male sex (OR 1.73, 95% CI 1.54-1.93, p < 0.00001), multifocality (OR 1.87, 95% CI 1.59-2.19, p < 0.00001), bilateral disease (OR 1.43, 95% CI 1.15-1.78, p < 0.001), capsular invasion (OR 1.67, 95% CI 1.10-2.54, p < 0.02), lymphovascular invasion (OR 4.89, 95% CI 2.76-8.66, p < 0.00001) and extra-thyroidal extension (OR 2.43, 95% CI 1.97-3.00, p < 0.00001). In addition, young age (< 45 years), male sex, multifocality, and extra-thyroidal extension were significantly associated with large-volume CLNM in clinically N0 DTC patients. However, the presence of Hashimoto's thyroiditis was not a predictors of large-volume CLNM. CONCLUSION: Young age (< 45 years), male sex, bilateral disease, multifocality, capsular invasion, lymphovascular invasion and extra-thyroidal extension are significantly associated with CLNM and pCND would be expected to have a higher yield in patients with these risk factors.

Using feasibility dose-volume histograms to reduce intercampus plan quality variability for head-and-neck cancer.

The purpose of this work is to objectively assess variability of intercampus plan quality for head-and-neck (HN) cancer and to test utility of a priori feasibility dose-volume histograms (FDVHs) as planning dose goals. In this study, 109 plans treated from 2017 to 2019 were selected, with 52 from the main campus and 57 from various regional centers. For each patient, the planning computed tomography images and contours were imported into a commercial program to generate FDVHs with a feasibility value (f-value) ranging from 0.0 to 0.5. For 10 selected organs-at-risk (OARs), we used the Dice similarity coefficient (DSC) to quantify the overlaps between FDVH and clinically achieved DVH of each OAR and determined the f-value associated with the maximum DSC (labeled as f-max). Subsequently, 10 HN plans from the regional centers were replanned with planning dose goals guided by FDVHs. The clinical and feasibility-guided auto-planning (FgAP) plans were evaluated using our institutional criteria. Among plans from the main campus and regional centers, the median f-max values were statistically significantly different (p < 0.05) for all OARs except for the left parotid (p = 0.622), oral cavity (p = 0.057), and mandible (p = 0.237). For the 10 FgAP plans, the median values of f-max were 0.21, compared to 0.37 from the clinical plans. With comparable dose coverage to the tumor volumes, the significant differences (p < 0.05) in the median f-max and corresponding dose reduction (shown in parenthesis) for the spinal cord, larynx, supraglottis, trachea, and esophagus were 0.27 (8.5 Gy), 0.3 (7.6 Gy), 0.19 (5.9 Gy), 0.19 (8.9 Gy), and 0.12 (4.0 Gy), respectively. In conclusion, the FDVH prediction is an objective quality assurance tool to evaluate the intercampus plan variability. This tool can also provide guideline in planning dose goals to further improve plan quality.

Depletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration.

Muscle regeneration requires the coordination of muscle stem cells, mesenchymal fibro-adipogenic progenitors (FAPs), and macrophages. How macrophages regulate the paracrine secretion of FAPs during the recovery process remains elusive. Herein, we systemically investigated the communication between CD206+ M2-like macrophages and FAPs during the recovery process using a transgenic mouse model. Depletion of CD206+ M2-like macrophages or deletion of CD206+ M2-like macrophages-specific TGF-ß1 gene induces myogenesis and muscle regeneration. We show that depletion of CD206+ M2-like macrophages activates FAPs and activated FAPs secrete follistatin, a promyogenic factor, thereby boosting the recovery process. Conversely, deletion of the FAP-specific follistatin gene results in impaired muscle stem cell function, enhanced fibrosis, and delayed muscle regeneration. Mechanistically, CD206+ M2-like macrophages inhibit the secretion of FAP-derived follistatin via TGF-ß signaling. Here we show that CD206+ M2-like macrophages constitute a microenvironment for FAPs and may regulate the myogenic potential of muscle stem/satellite cells.

An Overview on Rumex dentatus L.: Its Functions as a Source of Nutrient and Health-Promoting Plant.

Rumex dentatus L. (Polygonaceae), also known as toothed dock or Aegean dock, is a medicinal plant with a high culinary value in addition to being used as an ethnomedicinal plant. This review focuses on the botanical, nutritional, phytochemical, and pharmacological activities of R. dentatus, as well as the future prospects for systematic investigations into these areas. R. dentatus has been subjected to scientific evaluation, which has confirmed its traditional uses and demonstrated a wide range of biological and pharmacological potentials, including antioxidant, anticancer, antifungal, antibacterial, anti-inflammatory, and other biological properties. Phytochemical analyses showed the presence of anthraquinones, chromones, flavonoids, and essential oils. As a result of this current review, the medicinal significance of R. dentatus has been confirmed, and future research on its unexplored aspects, such as the identification of pharmacologically active chemical constituents and related mechanisms and safety, may be stimulated, with the goal of developing it into a drug.

Lithium toxicity following Roux-en-Y gastric bypass: Mini review and illustrative case.

Lithium is among the mainstays of treatment for bipolar disorder. Bariatric surgery can considerably change the oral bioavailability of drugs, particularly lithium. In this review, a 36-year-old male patient is described, who presented with lithium toxicity, including neurologic and gastric symptoms after undergoing Roux-en-Y gastric bypass. The mechanism of lithium toxicity is discussed; recommendations for clinicians regarding lithium use in postsurgical patients are provided; and previous case reports of lithium toxicity post-gastric bypass surgery are analyzed. Awareness and education of lithium absorption changes postbariatric surgery is essential for optimal patient care. Close clinical and drug concentration level monitoring is warranted.

A Scoping Review of Vaping, E-Cigarettes and Mental Health Impact: Depression and Suicidality.

Electronic cigarettes have grown in popularity due to natural curiosity, novel flavors, and advertising as both a means to aid smoking cessation and a "safe" smoking option. There is a substantial body of research on the harmful physical health effects of vaping, but there are relatively few studies on its mental health effects, particularly in adolescents 10-21 years of age. The purpose of this review is to examine the negative effects of vaping on mental health, in particular depression and suicidality. Using the databases PubMed, Scopus, Cochrane Library, and the search engine Google Scholar, we focused on observational studies looking into association between vaping, depression and suicidality. We found 7255 studies; after removing duplicates and other irrelevant articles, 106 articles were left. After reviewing the abstracts and titles, 99 citations were manually removed, 7 studies were included in the final review. Suicide attempts were significantly higher among e-cigarette users compared to non-users. E-cigarette use was associated with depression, suicidal ideation and suicide attempt. Suicide attempts were significantly higher among e-cigarette users compared to non-users. It is critical to raise awareness about the association between electronic cigarettes and adolescent mental health.

A new ent-clerodane diterpene from Detarium microcarpum Guill. & Perr. and its protective potential for osteoporosis.

A new clerodane diterpene, named 6α-hydroxy-3,13E-clerodien-15-oic acid (1), together with a known clerodane diterpene (2), four known labdane diterpenes (3-6), a triterpenoid (7), a known steroid (8), and two benzenoid compounds (9 and 10) were isolated from Detarium microcarpum Guill. & Perr. The structures of all obtained compounds were determined by chemical properties and spectroscopic evidence, accompanied by comparisons with data in the literature. Electronic circular dichroism (ECD) was performed for compounds 1-4 to confirm the absolute configuration. Compounds 1-3 and 8-10 were evaluated for the protective effect on osteoblasts. Compound 1 was observed to increase the proliferation of dexamethasone (DEX)-treated MC3T3-E1 cells significantly at 1 µM, which was comparable with the positive control geniposide at 10 µM. The results were further confirmed by flow cytometry analysis. In addition, compound 1 increased the level of alkaline phosphatase (ALP) and mineralization in osteoblasts inhibited by DEX. Moreover, Compound 9 (vanillic acid) showed a pronounced inhibition (IC50 6.5 ± 0.6 µM) on reactive oxygen species (ROS) production, and 10 (4-O-methyl gallic acid) showed a good inhibition with IC50 as 103.3 ± 2.2 µM, compared with the standard drug ibuprofen (IC50 54.2 ± 9.2 µM). Besides, compounds 1-3 and 8-10 were non-cytotoxic against MCF-7, NCI-H460, Hela, and BJ cell lines.

AMYPred-FRL is a novel approach for accurate prediction of amyloid proteins by using feature representation learning.

Amyloid proteins have the ability to form insoluble fibril aggregates that have important pathogenic effects in many tissues. Such amyloidoses are prominently associated with common diseases such as type 2 diabetes, Alzheimer's disease, and Parkinson's disease. There are many types of amyloid proteins, and some proteins that form amyloid aggregates when in a misfolded state. It is difficult to identify such amyloid proteins and their pathogenic properties, but a new and effective approach is by developing effective bioinformatics tools. While several machine learning (ML)-based models for in silico identification of amyloid proteins have been proposed, their predictive performance is limited. In this study, we present AMYPred-FRL, a novel meta-predictor that uses a feature representation learning approach to achieve more accurate amyloid protein identification. AMYPred-FRL combined six well-known ML algorithms (extremely randomized tree, extreme gradient boosting, k-nearest neighbor, logistic regression, random forest, and support vector machine) with ten different sequence-based feature descriptors to generate 60 probabilistic features (PFs), as opposed to state-of-the-art methods developed by a single feature-based approach. A logistic regression recursive feature elimination (LR-RFE) method was used to find the optimal m number of 60 PFs in order to improve the predictive performance. Finally, using the meta-predictor approach, the 20 selected PFs were fed into a logistic regression method to create the final hybrid model (AMYPred-FRL). Both cross-validation and independent tests showed that AMYPred-FRL achieved superior predictive performance than its constituent baseline models. In an extensive independent test, AMYPred-FRL outperformed the existing methods by 5.5% and 16.1%, respectively, with accuracy and MCC of 0.873 and 0.710. To expedite high-throughput prediction, a user-friendly web server of AMYPred-FRL is freely available at http://pmlabstack.pythonanywhere.com/AMYPred-FRL . It is anticipated that AMYPred-FRL will be a useful tool in helping researchers to identify new amyloid proteins.

Is adaptive planning necessary for patients with large tumor position displacements observed on daily image guidance during lung SBRT?

For patients undergoing stereotactic body radiation therapy for lung cancer, their tumor positions may vary due to anatomical changes. This study is to investigate whether adaptive re-planning is necessary for patients with large tumor position displacements observed from daily kV-cone-beam computed tomography (kV-CBCT). We selected 16 fractions from 16 patients with recorded treatment couch shifts greater than 1.5 cm under kV-CBCT guidance. The treatment positions for these patients were manually restored in kV-CBCTs via bone-to-bone alignments (B2B) and tumor-to-tumor alignments (T2T) with corresponding planning CTs. The tumor volumes, including PTVs, ITVs, and GTVs, were transferred from the planning CTs to these kV-CBCTs. With the planned beam configurations and treatment isocenters, kV-CBCTs were imported into the treatment planning system for dose recalculations. To minimize uncertainties of the Hounsfield Unit (HU) in kV-CBCTs, uniformed HU values were assigned to the externals, ITVs, and lungs. The percentage volumes of GTVs, ITVs, and PTVs receiving the prescription dose (VRx) and the dose to the normal structures were analyzed. Seven out of the 16 patients were identified with >5mm tumor position displacements after subtracting the recorded couch shifts from the shifts of B2B alignment. For T2T alignments, 9 out of 16 (56.3%) patients had VRx of PTV <95% (the planning goal) with 91.4% as the lowest, while VRx of the GTV and ITV remained 100% for all 16 patients. For B2B alignments, 14 out of 16 (87.5%) patients have VRx of PTV <95%; 5 patients (31.3%) had VRx of ITV <95%; and 4 patients (25.0%) had VRx of GTV <99%. T2T alignment with 5 mm PTV margin was found superior to B2B alignment, resulting in adequate dose coverage to the ITVs, even for tumors with large positional changes. Adaptive re-planning may not be necessary under these scenarios.

Arsenic contamination, induced symptoms, and health risk assessment in groundwater of Lahore, Pakistan.

The purpose of this study is to evaluate the arsenic concentration and related health risks in groundwater extracted from tube wells. The physicochemical parameters, including arsenic (As), were investigated using standard procedures. The parameters were found within the permissible limits except for arsenic, which was 78 µg/L. Unfortunately, 82% of the collected water samples were found contaminated with arsenic and exceeded the permissible limit set by the world health organization (10 µg/L). The water intake and its relationship between arsenic concentration, time, and induced symptoms in the study area residents were observed. Skin pigmentation, skin irritation, and numbness of the body were recognized as the major symptoms, and these symptoms were significantly correlated with p-value ˂ 0.05. In comparison, individuals who intake As-contaminated water (> 50 µg/L) for a duration of > 20 years show severe symptoms. Furthermore, health risk assessment associated with arsenic in terms of chronic daily intake (CRI), hazard quotient (HQ), and cancer risk assessment probability (CR) in groundwater was also studied. The HQ of arsenic was 7.46, and the CR value of As on Ravi road was as high as 0.00149, which indicates a possibility of cancer risk in the community Ravi road, Lahore. Based on the findings, the study area needs special monitoring and management of groundwater to reduce health risks associated with contaminated drinking water. Moreover, suitable remediation methods for removing arsenic should be adopted to avoid arsenic exposure and related health risks.