Natural Language Processing-Assisted Classification Models to Confirm Monoclonal Gammopathy of Undetermined Significance and Progression in Veterans' Electronic Health Records.

PURPOSE: To develop and validate natural language processing (NLP)-assisted machine learning (ML)-based classification models to confirm diagnoses of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) from electronic health records (EHRs) in the Veterans Health Administration (VHA). MATERIALS AND METHODS: We developed precompiled lexicons and classification rules as features for the following ML classifiers: logistic regression, random forest, and support vector machines (SVMs). These features were trained on 36,044 EHR documents from a random sample of 400 patients with at least one International Classification of Disease code for MGUS diagnosis from 1999 to 2021. The best-performing feature combination was calibrated in the validation set (17,826 documents/200 patients) and evaluated in the testing set (9,250 documents/100 patients). Model performance in diagnosis confirmation was compared with manual chart review results (gold standard) using recall, precision, accuracy, and F1 score. For patients correctly labeled as disease-positive, the difference between model-identified diagnosis dates and the gold standard was also computed. RESULTS: In the testing set, the NLP-assisted classification model using SVMs achieved best performance in both MGUS and MM confirmation with recall/precision/accuracy/F1 of 98.8%/93.3%/93.0%/96.0% for MGUS and 100.0%/92.3%/99.0%/96.0% for MM. Dates of diagnoses matched (±45 days) with those of gold standard in 73.0% of model-confirmed MGUS and 84.6% of model-confirmed MM. CONCLUSION: An NLP-assisted classification model can reliably confirm MGUS and MM diagnoses and dates and extract laboratory results using automated interpretation of EHR data. This algorithm has the potential to be adapted to other disease areas in VHA EHR system.

Progress on Sustainable Development Goal indicators in 707 districts of India: a quantitative mid-line assessment using the National Family Health Surveys, 2016 and 2021.

Background: India has committed itself to accomplishing the Sustainable Development Goals (SDGs) by 2030. Meeting these goals would require prioritizing and targeting specific areas within India. We provide a mid-line assessment of the progress across 707 districts of India for 33 SDG indicators related to health and social determinants of health. Methods: We used data collected on children and adults from two rounds of the National Family Health Survey (NFHS) conducted in 2016 and 2021. We identified 33 indicators that cover 9 of the 17 official SDGs. We used the goals and targets outlined by the Global Indicator Framework, Government of India and World Health Organization (WHO) to determine SDG targets to be met by 2030. Using precision-weighted multilevel models, we estimated district mean for 2016 and 2021, and using these values, computed the Annual Absolute Change (AAC) for each indicator. Using the AAC and targets, we classified India and each district as: Achieved-I, Achieved-II, On-Target and Off-Target. Further, when a district was Off-Target on a given indicator, we further identified the calendar year in which the target will be met post-2030. Findings: India is not On-Target for 19 of the 33 SDGs indicators. The critical Off-Target indicators include Access to Basic Services, Wasting and Overweight Children, Anaemia, Child Marriage, Partner Violence, Tobacco Use, and Modern Contraceptive Use. For these indicators, more than 75% of the districts were Off-Target. Because of a worsening trend observed between 2016 and 2021, and assuming no course correction occurs, many districts will never meet the targets on the SDGs even well after 2030. These Off-Target districts are concentrated in the states of Madhya Pradesh, Chhattisgarh, Jharkhand, Bihar, and Odisha. Finally, it does not appear that Aspirational Districts, on average, are performing better in meeting the SDG targets than other districts on majority of the indicators. Interpretation: A mid-line assessment of districts' progress on SDGs suggests an urgent need to increase the pace and momentum on four SDG goals: No Poverty (SDG 1), Zero Hunger (SDG 2), Good Health and Well-Being (SDG 3) and Gender Equality (SDG 5). Developing a strategic roadmap at this time will help India ensure success with regards to meeting the SDGs. India's emergence and sustenance as a leading economic power depends on meeting some of the more basic health and social determinants of health-related SDGs in an immediate and equitable manner. Funding: This work was funded by the Bill and Melinda Gates Foundation, INV-002992.

Lemon grass essential oil improves Gladiolus grandiflorus postharvest life by modulating water relations, microbial growth, biochemical activity, and gene expression.

Gladiolus (Gladiolus grandiflorus Andrews) is a high-valued bulbous cut flower. However, the shorter postharvest life of the gladiolus, limits its marketing and commercial value. In the present investigation, the effect of lemon grass (LG) essential oil as an antimicrobial agent was studied towards increasing the vase life of gladiolus. The results revealed that as compared to control (distilled water), treatment with a lower concentration of 5 µL L-1 LG essential oil prolonged the vase life of gladiolus up to 11 days (d). Scanning Electron Microscope (SEM) observation indicated that the sample treated with 5 µL L-1 LG essential oil showed intact vasculature, suggesting reduced microbial blockage at the stem end which was further corroborated by microbial count. Biochemical analysis suggested an increased level of total soluble sugars, carotenoid content, lower MDA accumulation, and higher activity of antioxidant enzymes in LG treated flowers. Moreover, transcripts levels of genes associated with senescence viz., GgCyP1 and GgERS1a were downregulated, while expression of GDAD1 and antioxidant genes such as GgP5C5, GgPOD 1, GgMnSOD, and GgCAT1 were upregulated in LG treated cut spikes as compared to control. Among various treatments we have concluded that, the vase life of the gladiolus cut spike was improved along with the relative fresh flower weight and diameter of flower at the lower dose of 5 µL L-1 LG oil in the vase solution. Thus, LG oil as an eco-friendly agent has the potential to extend the postharvest life of cut flowers.

Anaesthesia for tracheal resection and anastomosis.

Tracheal resection anastomosis is one of the most challenging surgeries. Notable advances in this field have made possible a variety of surgical, anesthetic, and airway management options. There are reports of newer approaches ranging from use of supraglottic airway devices, regional anesthesia, and extracorporeal support. Endotracheal intubation with cross-field ventilation and jet ventilation are the standard techniques for airway management followed. These call for multidisciplinary preoperative planning and close communication during surgery and recovery. This review highlights the anesthetic challenges faced during tracheal resection and anastomosis with specific considerations to preoperative workup, classification of tracheal stenosis, airway management, ventilation strategies, and extubation. The newer advances proposed have been reviewed.

Selective Depletion of ZAP-Binding CpG Motifs in HCV Evolution.

Hepatitis C virus (HCV) is a bloodborne pathogen that can cause chronic liver disease and hepatocellular carcinoma. The loss of CpGs from virus genomes allows escape from restriction by the host zinc-finger antiviral protein (ZAP). The evolution of HCV in the human host has not been explored in the context of CpG depletion. We analysed 2616 full-length HCV genomes from 1977 to 2021. During the four decades of evolution in humans, we found that HCV genomes have become significantly depleted in (a) CpG numbers, (b) CpG O/E ratios (i.e., relative abundance of CpGs), and (c) the number of ZAP-binding motifs. Interestingly, our data suggests that the loss of CpGs in HCV genomes over time is primarily driven by the loss of ZAP-binding motifs; thus suggesting a yet unknown role for ZAP-mediated selection pressures in HCV evolution. The HCV core gene is significantly enriched for the number of CpGs and ZAP-binding motifs. In contrast to the rest of the HCV genome, the loss of CpGs from the core gene does not appear to be driven by ZAP-mediated selection. This work highlights CpG depletion in HCV genomes during their evolution in humans and the role of ZAP-mediated selection in HCV evolution.

Predictors of Anastomotic Complications After Resection and Anastomosis for Tracheal Stenosis.

Resection and anastomosis is an effective option for the management of complex tracheal stenosis, however, it's not without the complications. This study aims at evaluating various factors predicting anastomotic complications after trachea resection and anastomosis. This is a retrospective analysis of database from a dedicated thoracic surgical unit in New Delhi, India over 7 years. An analysis of demographic details, perioperative variables including complications were carried out. Analysis of various factors predicting anastomotic complications was performed. Out of 65 patients in the study, 49 (75.3%) were males and 16 (24.7%) were females. Median age of the patients was 31 years. Stenosis was cervical in 80%, cervico-thoracic in 15.4% and thoracic in 4.6% of patients. Median length of stenosis was 2.9 cm (1-4.2). 53 (81.6%) patients had some kind of preoperative intervention, where as rest 12 (18.4%) patients had no intervention at all. Out of 65 patients, 26 (40%) had crico-tracheal anastomosis while 39 (60%) had tracheo-tracheal anastomosis. Median length of resected tracheal segment was 3.3 cm (1-5). Overall complication rate (anastomotic + non-anastomotic) was 18.4% in which anastomosis related were in 4 (6.1%) patients. Resection of tracheal segment ≥ 3.5 cm, presence of diabetes mellitus and pre-operative use of corticosteroids were statistically significant factors for the onset of complications. Perioperative mortality rate was 1.5% (n = 1). Length of resection > 3.5 cm, presence of diabetes mellitus and pre-operative prolonged use of corticosteroids were significant predictors for the anastomotic complications.

Poly (Lactic-co-Glycolic Acid) & Tocopheryl Polyethylene Glycol Succinate Nanoparticles for the Treatment of Different Brain Cancers.

Nanotechnology and material science developments emerge in the manufacturing of various novel modes of drug delivery, which have proven scientifically promising. Polymer nanoparticles have high stability, high specificity, high drug-carrying power, control release, and potential to be used in various pathways. They usually supply hydrophilic and hydrophobic molecules with medicines. In this review, we have discussed the different types of brain tumour, different PLGA (Poly Lactic-co-Glycolic Acid) nanostructures, PLGA in brain tumour targeting, and the recent advancement of PLGA based nanoparticles. This review focused on the method of preparation of polymeric nanoparticles, the significance of EPR (Enhanced Permeability and Retention) effect with PLGA, the significance of TPGS in cancer, and discussed the pharmaceutical application of PLGA nanoparticles. We expect these polymeric nanoparticles will be very successful and efficient for disease targeting in the future and new techniques will emerge.

Lung preservation in mucoepidermoid carcinoma of tracheobronchial tree: A case series.

INTRODUCTION: Mucoepidermoid carcinoma (MEC) is a primary salivary gland tumor also arising from nonsalivary gland organs of the body such as submucosal glands of tracheobronchial tree. Surgical resection with negative margins is the treatment of choice. All efforts should be made to preserve as much lung parenchyma as possible, by various bronchoplastic procedures. We present our experience with mucoepidermoid tumors and review their management options including lung preservation techniques and outcome of surgery. MATERIALS AND METHODS: This is a retrospective analysis of prospectively maintained data of 14 patients who underwent surgery for MEC. Their demographic data; clinical presentation; and preoperative, intraoperative, and postoperative details were recorded. All patients underwent contrast-enhanced computed tomography of chest and bronchoscopy as part of workup for diagnosis and to assess the location, size, and extent of tumor; extraluminal component; and status of distal lung parenchyma. RESULTS: There were eight male and six female patients. The median age at the time of surgery was 28.36 years (range 22-45 years). The procedures performed included right upper lobectomy and right pneumonectomy in one patient each, left main bronchus sleeve resection in six patients, left upper sleeve lobectomy in three patients, and carinal resection and reconstruction of neo carina in three patients. Twelve (85.7%) of our patients underwent lung-preserving surgery. The median hospital stay and chest tube removal duration was 4 and 3 days, respectively. The median tumor size was 1.91 cm (range 1-8 cm). The median follow-up was 24 months (ranging from 6 to 78 months). CONCLUSION: Radical surgery to achieve R "0" resection with aggressive emphasis on lung preservation is the mainstay of treatment of MEC. Greater awareness of these tumors is necessary to avoid misdiagnosis and to prevent delaying of potential complete resection of MEC.

Withdrawal Notice: The Recent Advancement in the Field of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) for Aiming Breast Cancer

The article has been withdrawn at the request of the authors and editor of the journal Current Drug MetabolismBentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Association Between Institutional Social Media Involvement and Gastroenterology Divisional Rankings: Cohort Study.

BACKGROUND: Patients often look to social media as an important tool to gather information about institutions and professionals. Since 1990, United States News and World Report (USNWR) has published annual rankings of hospitals and subspecialty divisions. It remains unknown if social media presence is associated with the USNWR gastroenterology and gastrointestinal (GI) surgery divisional rankings, or how changes in online presence over time affects division ranking. OBJECTIVE: The objective of this study was to determine if social media presence is associated with USNWR gastroenterology and GI surgery divisional rankings and to ascertain how changes in online presence over time affect division rankings. METHODS: Social media presence among the top 30 institutions listed in the 2014 USNWR gastroenterology and GI surgery divisional rankings were assessed using Pearson's correlation coefficients and multivariate analysis, controlling for covariates. Linear and logistic regression using data from 2014 and 2016 USNWR rankings were then used to assess the association between institutional ranking or reputation score with any potential changes in numbers of followers over time. Sensitivity analysis was performed by assessing the area under the receiver operating characteristic curve to determine the follower threshold associated with improved or maintained ranking, which was done by dichotomizing changes in followers at values between the 7000 and 12,000 follower mark. RESULTS: Twitter follower count was an independent predictor of divisional ranking (ß=.00004; P<.001) and reputation score (ß=-.00002; P=.03) in 2014. Academic affiliation also independently predicted USNWR division ranking (ß=5.3; P=.04) and reputation score (ß=-7.3; P=.03). Between 2014 and 2016, Twitter followers remained significantly associated with improved or maintained rankings (OR 14.63; 95% CI 1.08-197.81; P=.04). On sensitivity analysis, an 8000 person increase in Twitter followers significantly predicted improved or maintained rankings compared to other cutoffs. CONCLUSIONS: Institutional social media presence is independently associated with USNWR divisional ranking and reputation score. Improvement in social media following was also independently associated with improved or maintained divisional ranking and reputation score, with a threshold of 8000 additional followers as the best predictor of improved or stable ranking.

A non-canonical autophagy-dependent role of the ATG16L1T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence.

50% of Caucasians carry a Thr300Ala variant (T300A) in the protein encoded by the macroautophagy/autophagy gene ATG16L1. Here, we show that the T300A variant confers protection against urinary tract infections (UTIs), the most common infectious disease in women. Using knockin mice carrying the human T300A variant, we show that the variant limits the UTI-causing bacteria, uropathogenic Escherichia coli (UPEC), from establishing persistent intracellular reservoirs, which can seed UTI recurrence. This phenotype is recapitulated in mice lacking Atg16l1 or Atg7 exclusively in the urothelium. We further show that mice with the T300A variant exhibit urothelial cellular abnormalities, including vesicular congestion and aberrant accumulation of UPK (uroplakin) proteins. Importantly, presence of the T300A variant in humans is associated with similar urothelial architectural abnormalities, indicating an evolutionarily conserved impact. Mechanistically, we show that the reduced bacterial persistence is independent of basal autophagic flux or proinflammatory cytokine responses and does not involve Atg14 or Epg5. However, the T300A variant is associated with increased expression of the small GTPase Rab33b; RAB33B interacts with ATG16L1, as well as other secretory RABs, RAB27B and RAB11A, important for UPEC exocytosis from the urothelium. Finally, inhibition of secretory RABs in bladder epithelial cells increases intracellular UPEC load. Together, our results reveal that UPEC selectively utilize genes important for autophagosome formation to persist in the urothelium, and that the presence of the T300A variant in ATG16L1 is associated with changes in urothelial vesicle trafficking, which disrupts the ability of UPEC to persist, thereby limiting the risk of recurrent UTIs. Abbreviations: 3-PEHPC: 3-pyridinyl ethylidene hydroxyl phosphonocarboxylate; ATG: autophagy; ATG16L1: autophagy related 16 like 1; BECs: bladder epithelial cells; dpi: days post infection; hpi: hours post infection; IF: immunofluorescence; IL1B: interleukin 1 beta; IL6: interleukin 6; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MVB: multivesicular bodies; T300A: Thr300Ala; TNF: tumor necrosis factor; QIR(s): quiescent intracellular reservoir(s); siRNA: short interfering RNA; UPEC: uropathogenic Escherichia coli; UTI(s): urinary tract infection(s); TEM: transmission electron microscopy; WT: wild type.

High-Flow Vascular Malformation of Ear: A Case Report.

Vascular anomalies are categorized into vascular tumours or vascular malformations on the basis of clinical features and histopathology. The literature regarding high flow arteriovenous malformations of the auricle is rare. A case of a patient clinically diagnosed with an arteriovenous malformation of the external ear and was managed with preoperative embolization, surgical excision and reconstruction of ear with split thickness skin graft, is presented. The pathogenesis, clinical presentation, diagnostic work up, radiological intervention and management options regarding arteriovenous malformations are discussed. Total cure is an illusion and rarely achieved in high flow high grade vascular malformation with nearly 98% recurrence reported in 5 years. Patient followed for next 3 months with no evidence of recurrence.

Intraoperative partial pressure of oxygen measurement to predict flap survival.

INTRODUCTION: Flap monitoring using partial pressure of oxygen (pO2) is a proven modality. Instruments needed are expensive and are not readily available to a clinician. Here, pO2 of flap has been determined using readily available and cheap methods, and a cut-off value is calculated which helps in predicting flap outcome. METHODS AND RESULTS: Total 235 points on 84 skin flaps were studied. Capillary blood was collected from flap and fingertip using 1-ml syringes after at least 30 min of flap inset, and pO2 analysed using blood gas analyser. Fall/change of pO2 (difference of mean of pO2 [diff-pO2]) was also calculated by subtracting the flap pO2 from the finger pO2. Flap was monitored clinically in post-operative period and divided into two groups depending on its survival with Group 1 - dead points and Group 2 - alive points. pO2 and diff-pO2 amongst both the groups were compared and found to be statistically different (P = 0.0001). Cut-off value calculated for pO2 was found to be <86.3 mmHg with a sensitivity of 100% and specificity of 89.05%. The difference of >68.503 mmHg of flap pO2 compared from finger pO2 was calculated as a cut-off with sensitivity of 94.12 and specificity of 79.60%. CONCLUSIONS: Flap areas having intra-operative pO2 value <86.3 mmHG have higher chances (60.71%) of getting necrosis later. Similarly, if diff-pO2 compared to fingertip is >68.5 mmHg, chances of those points getting necrosed in post-operative period are high.

The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease.

INTRODUCTION: Metallothioneins (MTs) are a class of ubiquitously occurring low-molecular-weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. MT-3 exhibits neuro-inhibitory activity. The possibility to enhance the expression of MT-3 or protect it from degradation is an attractive therapeutic target, because low levels of MT-3 were found in brains of Alzheimer's disease (AD) patients. OBJECTIVES: The primary objective of this study was to test an enhancement of MT-3 cellular concentration after MT-3 binding treatment, which could prevent MT-3 degradation. METHODS: MTT assay, flow-cytometry, fluorescence microscopy, quantitative real-time polymerase chain reaction, and immunodetection of MT3 were used for analysis of effect of STOCK1N-26544, STOCK1N-26929, and STOCK1N-72593 on immortalized human microglia-SV40 cell line. RESULTS: All three tested compounds enhanced concentration of MT-3 protein in cells and surprisingly also mRNA concentration. IC50 values of tested molecules exceeded about ten times the concentration that was needed for induction of MT-3 expression. The tested compound Benzothiazolone-2 enhanced apoptosis and necrosis, but it was not of severe effect. About 80% of cells were still viable. There was no serious ROS-generation and no severe decrease in mitochondria numbers or stress induced endoplasmic reticulum changes after test treatments. The selected compound showed stable hydrophobic and electrostatic interaction during MT-3 ligand interaction. CONCLUSION: Benzothiazolone-2 compounds significantly enhanced MT-3 protein and mRNA levels. The compounds can be looked upon as one of the probable lead compounds for future drug designing experiments in the treatment of Alzheimer's disease.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Structural investigations into the binding mode of novel neolignans Cmp10 and Cmp19 microtubule stabilizers by in silico molecular docking, molecular dynamics, and binding free energy calculations.

Microtubule stabilizers provide an important mode of treatment via mitotic cell arrest of cancer cells. Recently, we reported two novel neolignans derivatives Cmp10 and Cmp19 showing anticancer activity and working as microtubule stabilizers at micromolar concentrations. In this study, we have explored the binding site, mode of binding, and stabilization by two novel microtubule stabilizers Cmp10 and Cmp19 using in silico molecular docking, molecular dynamics (MD) simulation, and binding free energy calculations. Molecular docking studies were performed to explore the ß-tubulin binding site of Cmp10 and Cmp19. Further, MD simulations were used to probe the ß-tubulin stabilization mechanism by Cmp10 and Cmp19. Binding affinity was also compared for Cmp10 and Cmp19 using binding free energy calculations. Our docking results revealed that both the compounds bind at Ptxl binding site in ß-tubulin. MD simulation studies showed that Cmp10 and Cmp19 binding stabilizes M-loop (Phe272-Val288) residues of ß-tubulin and prevent its dynamics, leading to a better packing between α and ß subunits from adjacent tubulin dimers. In addition, His229, Ser280 and Gln281, and Arg278, Thr276, and Ser232 were found to be the key amino acid residues forming H-bonds with Cmp10 and Cmp19, respectively. Consequently, binding free energy calculations indicated that Cmp10 (-113.655 kJ/mol) had better binding compared to Cmp19 (-95.216 kJ/mol). This study provides useful insight for better understanding of the binding mechanism of Cmp10 and Cmp19 and will be helpful in designing novel microtubule stabilizers.

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease.

MOTIVATION: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimer's disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. RESULTS: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.