Hyperbolic Lattices and Two-Dimensional Yang-Mills Theory.

Hyperbolic lattices are a new type of synthetic quantum matter emulated in circuit quantum electrodynamics and electric-circuit networks, where particles coherently hop on a discrete tessellation of two-dimensional negatively curved space. While real-space methods and a reciprocal-space hyperbolic band theory have been recently proposed to analyze the energy spectra of those systems, discrepancies between the two sets of approaches remain. In this work, we reconcile those approaches by first establishing an equivalence between hyperbolic band theory and U(N) topological Yang-Mills theory on higher-genus Riemann surfaces. We then show that moments of the density of states of hyperbolic tight-binding models correspond to expectation values of Wilson loops in the quantum gauge theory and become exact in the large-N limit.

Molecular hybridization, synthesis, in vitro α-glucosidase inhibition, in vivo antidiabetic activity and computational studies of isatin based compounds.

In the pursuit of novel antidiabetic agents, a series of isatin-thiazole derivatives (7a-7j) were synthesized and characterized using a range of spectroscopic techniques. The enzyme inhibitory activities of the target analogues were assessed using both in vitro and in vivo assays. The tested compounds 7a-7j demonstrated In vitro inhibitory potential against α-glucosidase, as indicated by their IC50 values ranging from 28.47 to 46.61 µg/ml as compared to standard drug acarbose IC50 value of 27.22 ± 2.30 µg/ml. Additionally, compounds 7d and 7i were chosen for in vivo evaluation of their antidiabetic efficacy in streptozotocin-induced diabetic Wistar rats. These compounds exhibited significant antidiabetic activity both in vitro and in vivo, compound 7d produces therapeutic effects compared to standard pioglitazone by decreasing glycaemia and triglyceride levels in diabetic animals. Furthermore, a molecular docking study was conducted to elucidate the binding interactions of the compounds within the α-glucosidase enzyme binding pocket (PDB ID 3A47) and stability was confirmed by dynamics simulation trajectories. Thus, from the above findings, it may demonstrate that isatin-thiazole hybrids constitute promising candidates in the pursuit of developing newer oral antidiabetic agents.

Characterization of spatial-temporal distribution and microenvironment source contribution of PM2.5 concentrations using a low-cost sensor network with artificial neural network/kriging techniques.

Low-cost sensors (LCS) network is widely used to improve the resolution of spatial-temporal distribution of air pollutant concentrations in urban areas. However, studies on air pollution sources contribution to the microenvironment, especially in industrial and mix-used housing areas, still need to be completed. This study investigated the spatial-temporal distribution and source contributions of PM2.5 in the urban area based on 6-month of the LCS network datasets. The Artificial Neural Network (ANN) was used to calibrate the measured PM2.5 by the LCS network. The calibrated PM2.5 were shown to agree with reference PM2.5 measured by the BAM-1020 with R2 of 0.85, MNE of 30.91%, and RMSE of 3.73 µg/m3, which meet the criteria for hotspot identification and personal exposure study purposes. The Kriging method was further used to establish the spatial-temporal distribution of PM2.5 concentrations in the urban area. Results showed that the highest average PM2.5 concentration occurred during autumn and winter due to monsoon and topographic effects. From a diurnal perspective, the highest level of PM2.5 concentration was observed during the daytime due to heavy traffic emissions and industrial production. Based on the present ANN-based microenvironment source contribution assessment model, temples, fried chicken shops, traffic emissions in shopping and residential zones, and industrial activities such as the mechanical manufacturing and precision metal machining were identified as the sources of PM2.5. The numerical algorithm coupled with the LCS network presented in this study is a practical framework for PM2.5 hotspots and source identification, aiding decision-makers in reducing atmospheric PM2.5 concentrations and formulating regional air pollution control strategies.

Telehealth Potential in Pediatric Orthopaedics and Sports Medicine Care is Comparable to In-Person Care But Disparities Remain.

BACKGROUND: Understanding the challenges and potential of telehealth visits (THVs) in a large population can inform future practice and policy discussion for pediatric orthopaedic and sports medicine (OSM) care. We comprehensively assess telehealth challenges and potential in a large pediatric OSM population based on access, visit completion, patient satisfaction, and technological challenges. METHODS: Demographics, address, insurance, visit information, patient feedback, experience with video visits, and technical challenges of all 2019 to 2020 visits at our hospital were assessed (3,278,006 visits). We evaluated the differences in rate of telehealth utilization, rate of patient adherence, disparities in care access and patient satisfaction, and technological issues. RESULTS: Compared with in-person prepandemic visits, THVs had lower ratios of non-White patients (by 5.8%; P <0.001), Hispanic patients (by 2.8%; P <0.001) and patients with public insurance (by 1.8%; P <0.001), and a higher mean distance between the patient's residence and clinic (by 18.8 miles; P <0.001). There were minimal differences in median household income (average $2297 less in THV; P <0.001) and social vulnerability index (average 0.01 points lower in THV; P <0.001) between groups. THVs had comparable patient satisfaction to in-person visits. Non-White patients, Hispanics, and those with public insurance had lower ratings for both in-person visits and THVs and had more technical difficulties during their THV. CONCLUSIONS: Telehealth is a viable method of care for a range of pediatric OSM conditions, providing a similar quality of care as in-person visits with a greater geographic reach. However, in its current format, reduced disparities were not observed in pediatric OSM THVs. LEVEL OF EVIDENCE: Level III.

Comparative measurement of CO2, CH4 and CO at two traffic interjunctions having inflated vehicular flow in Delhi.

Vehicular emissions are considered one of the major anthropogenic sources of greenhouse gases and poor air quality in metropolitan cities. This study aims to see the correlation of CO2, CH4, and CO through monitoring over a period from December 2020 to October 2021 covering three seasons' winter, summer, and monsoon at two different traffic locations of Delhi having different traffic volumes, road patterns, and traffic management. The annual average morning concentration of CO2, CH4 and CO was found (533 ± 105), (7.3 ± 3.1), (10.7 ± 3.0) ppm at Najafgarh and (480 ± 70), (5.2 ± 1.8), (7.8 ± 2.8) ppm at Rajendra Place, respectively. A relationship between concentration of all three gases and meteorological parameters such as temperature, humidity, wind speed and wind direction has also been investigated using Pearson correlation coefficient and pollution rose diagram. A comparable pattern in concentration was observed for all three gases in spatial (location) and temporal (diurnal) distribution. The concentration trend of CO2 in different seasons is winter > summer > monsoon, while in the case of CH4 winter = summer > monsoon but not any seasonal trend was noted in CO case. It is observed that CO2 has a good relation with CO (a tracer for vehicular emission) in terms of diurnal variation, whereas, CH4 does not represent a relation with CO and CO2 diurnally, suggesting that vehicles are the source of CO2 but not much contributing to other greenhouse gases like CH4.

The influence of COVID-19 pandemic on PM2.5 air quality in Northern Taiwan from Q1 2020 to Q2 2021.

The study aimed to investigate the PM2.5 variations in different periods of COVID-19 control measures in Northern Taiwan from Quarter 1 (Q1) 2020 to Quarter 2 (Q2) 2021. PM2.5 sources were classified based on long-range transport (LRT) or local pollution (LP) in three study periods: one China lockdown (P1), and two restrictions in Taiwan (P2 and P3). During P1 the average PM2.5 concentrations from LRT (LRT-PM2.5-P1) were higher at Fuguei background station by 27.9% and in the range of 4.9-24.3% at other inland stations compared to before P1. The PM2.5 from LRT/LP mix or pure LP (Mix/LP-PM2.5-P1) was also higher by 14.2-39.9%. This increase was due to higher secondary particle formation represented by the increase in secondary ions (SI) and organic matter in PM2.5-P1 with the largest proportion of 42.17% in PM2.5 from positive matrix factorization (PMF) analysis. A similar increasing trend of Mix/LP-PM2.5 was found in P2 when China was still locked down and Taiwan was under an early control period but the rapidly increasing infected cases were confirmed. The shift of transportation patterns from public to private to avoid virus infection explicated the high correlation of the increasing infected cases with the increasing PM2.5. In contrast, the decreasing trend of LP-PM2.5-P3 was observed in P3 with the PM2.5 biases of ∼45% at all the stations when China was not locked down but Taiwan implemented a semi-lockdown. The contribution of gasoline vehicle sources in PM2.5 was reduced from 20.3% before P3 to 10% in P3 by chemical signatures and source identification using PMF implying the strong impact of strict control measures on vehicle emissions. In summary, PM2.5 concentrations in Northern Taiwan were either increased (P1 and P2) or decreased (P3) during the COVID-19 pandemic depending on control measures, source patterns and meteorological conditions.

Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Pyridine derivatives as anticancer lead compounds with Fatty Acid Synthase as the target: An in silico-guided in vitro study.

For the past few decades, structure-based drug discovery (SBDD) has become an inevitable technique in the drug development process for screening hit compounds against therapeutic targets. Here, we have successfully used the SBDD approach viz. virtual high-throughput screening to identify potential inhibitors against the Ketoacyl synthase (KS) domain of Fatty acid synthase (FASN). Overexpression of FASN, and subsequent enhancement of de novo lipogenesis is a key survival strategy of cancer cells. Hence, targeting lipid metabolism using FASN inhibitors has been considered as a promising method to induce metabolic stress, thereby posing a survival disadvantage to cancer cells. In the present study, we have successfully identified eight FASN inhibitors from Asinex Elite database by implementing in silico tools. Five of the hit compounds share a common ring structure, which enables characteristic binding interactions with FASN-KS. Among them, in vitro validation showed that SFA 22637550 possesses significant FASN inhibitory activity and antiproliferative effect in human cancer cells of various origins. The maximum sensitivity was exhibited towards HepG2 hepatocellular carcinoma cells (IC50 = 28 µM). The mode of cell death was found to be apoptosis with a significant increase in SubG0 population without affecting any other phases of the cell cycle. The current study puts forward an excellent core structure for the development of potent FASN inhibitors for successfully targeting cancer cell metabolism, thereby causing selective cell death.

Magnetoencephalographic imaging of ictal high-frequency oscillations (80-200 Hz) in pharmacologically resistant focal epilepsy.

OBJECTIVE: Specificity of ictal high-frequency oscillations (HFOs) in identifying epileptogenic abnormality is significant, compared to the spikes and interictal HFOs. The objectives of the study were to detect and to localize ictal HFOs by magnetoencephalography (MEG) for identifying the seizure onset zone (SOZ), evaluate the cortical excitability from preictal to ictal transition, and establish HFO concordance rates with other modalities and postsurgical resection. METHODS: Sixty-seven patients with drug-resistant epilepsy had at least 1 spontaneous seizure each during MEG acquisition, and analysis was carried out on 20 seizures from 20 patients. Ictal MEG data were bandpass filtered (80-200 Hz) to visualize, review, and analyze the HFOs co-occurring with ictal spikes. Source montages were generated on both hemispheres, mean fast Fourier transform was computed on virtual time series for determining the preictal to ictal spectral power transition, and source reconstruction was performed with sLORETA and beamformers. The concordance rates of ictal MEG HFOs (SOZ) was estimated with 4 reference epileptogenic regions. RESULTS: In each subject, transient bursts of high-frequency oscillatory cycles, distinct from the background activity, were observed in the periictal continuum. Time-frequency analysis showed significant spectral power surge (85-160 Hz) during ictal state (P < .05) compared to preictal state, but there was no variation in the peak HFO frequencies (P > .05) for each subgroup and at each source montage. HFO source localization was consistent between algorithms (k = 0.857 ± 0.138), with presumed epileptogenic zone (EZ) comparable to other modalities. In patients who underwent surgery (n = 6), MEG HFO SOZ was concordant with the presumed EZ and the surgical resection site (100%), and all were seizure-free during follow-up. SIGNIFICANCE: HFOs could be detected in the MEG periictal state, and its sources were accurately localized. During preictal to ictal transition, HFOs exhibited dynamic augmentation in intrinsic epileptogenicity. Spatial overlap of ictal HFO sources was consistent with EZ determinants and the surgical resection area.

Liquid chromatography/electrospray ionization tandem mass spectrometry study of repaglinide and its forced degradation products.

RATIONALE: Stress stability studies of drugs have been recognized as an essential part of the drug development process. These studies are used to investigate the intrinsic stability of the drugs and for the development of a selective stability indicating assay method (SIAM). Stress testing is also useful for the formulation and packaging development, shelf-life determination and designing of manufacturing processes. As per regulatory guidelines, stress degradation studies and structural characterization should be carried out to establish degradation pathways of the drug, which is essential from both the efficacy and safety point of view. As the stress stability studies of repaglinide have not been reported in the literature, the present study has been undertaken. METHODS: Repaglinide (RP), an oral anti-diabetic drug, was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress conditions as per International Conference on Harmonization (ICH) guidelines Q1A (R2). The chromatographic separation of the drug and its degradation products (DPs) was achieved on an Agilent XDB C-18 column using the gradient elution method with a mobile phase consisting of 20 mM ammonium acetate and acetonitrile at flow rate of 1.0 mL min-1 . The DPs were characterized using liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) in combination with accurate mass measurements. RESULTS: The drug degraded under hydrolytic and oxidative stress, while it was stable under thermal and photolytic stress conditions. In total, six DPs were formed and the LC/MS method described here can resolve all DPs from the parent as well as from each other under various stress conditions. To elucidate the structures of DPs, fragmentation of the [M + H]+ ions of RP and its DPs was studied by using LC/ESI-MS/MS combined with accurate mass measurements. CONCLUSIONS: The forced degradation of RP carried out as per ICH guidelines results in the formation of six degradation products which have been characterized using LC/MS/MS in combination with accurate mass measurements.

Three-component, one-pot synthesis of anthranilamide Schiff bases bearing 4-aminoquinoline moiety as Mycobacterium tuberculosis gyrase inhibitors.

An efficient three-component, one-pot protocol is described for the synthesis of biologically interesting 2-(benzylideneamino)-N-(7-chloroquinolin-4-yl)benzohydrazide derivatives from isatoic anhydride, 7-chloro-4-hydrazinylquinoline and aromatic and/or hetero aromatic aldehydes under catalyst free condensation by using water as reaction media. All synthesized compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis (MTB) and cytotoxicity activity against normal VERO cell lines. The synthesized compounds exhibited minimum inhibitory concentration (MIC) ranging from 0.78 to 25µM. Among the tested compounds 4c, 4o, 4r, and 4u exhibited promising inhibitory activity (MIC=3.12µM). Compounds 4h and 4i stand out, showing MIC values of 0.78 and 1.56µM respectively. Both compounds were further screened for their Mycobacterium tuberculosis DNA gyrase inhibitory assay which suggested that these compounds have a great potential for further optimization and development as antitubercular agents.

Bacterial Diversity Patterns Differ in Soils Developing in Sub-tropical and Cool-Temperate Ecosystems.

Microbial diversity patterns have been surveyed in many different soils and ecosystems, but we are unaware of studies comparing similar soils developing from similar parent materials in contrasting climates. In 2008, developmental chronosequences with ages ranging from 105 to 500,000 years across Georgia (GA) and Michigan (MI) were studied to investigate how bacterial community composition and diversity change as a result of local environmental gradients that develop during pedogenesis. Geographic factors were studied between and within locations spanning two scales: (1) regionally between 0.1 and 50 and (2) ∼1700 km apart. The diversity was surveyed using high-throughput pyrosequencing, and variance partitioning was used to describe the effects of spatial, environmental, and spatio-environmental factors on bacterial community composition. At the local scale, variation in bacterial communities was most closely related to environmental factors (rM = 0.59, p = 0.0001). There were differences in bacterial communities between the two locations, indicating spatial biogeography. Estimates of bacterial diversity were much greater in MI (numbers of OTU, ACE, and Chao1) and remained 2-3× greater in MI than GA after removing the effect of soil properties. The large differences in diversity between geographically separated bacterial communities in different climates need further investigation. It is not known if the rare members of the community, which contributed to greater bacterial diversity in GA relative to MI, play an important role in ecosystem function but has been hypothesized to play a role in ecosystem resiliency, resistance, and stability. Further research on the link between bacterial diversity and spatial variability related to climate needs further investigation.

From the bench to clinical practice: understanding the challenges and uncertainties in immunogenicity testing for biopharmaceuticals.

Unlike conventional chemical drugs where immunogenicity typically does not occur, the development of anti-drug antibodies following treatment with biologics has led to concerns about their impact on clinical safety and efficacy. Hence the elucidation of the immunogenicity of biologics is required for drug approval by health regulatory authorities worldwide. Published ADA 'incidence' rates can vary greatly between same-class products and different patient populations. Such differences are due to disparate bioanalytical methods and interpretation approaches, as well as a plethora of product-specific and patient-specific factors that are not fully understood. Therefore, the incidence of ADA and their association with clinical consequences cannot be generalized across products. In this context, the intent of this review article is to discuss the complex nature of ADA and key nuances of the methodologies used for immunogenicity assessments, and to dispel some fallacies and myths.

Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach.

Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment.

Molecular Markers of Secondary Organic Aerosol in Mumbai, India.

Biogenic secondary organic aerosols (SOA) are generally considered to be more abundant in summer than in winter. Here, polar organic marker compounds in urban background aerosols from Mumbai were measured using gas chromatography-mass spectrometry. Surprisingly, we found that concentrations of biogenic SOA tracers at Mumbai were several times lower in summer (8-14 June 2006; wet season; n = 14) than in winter (13-18 February 2007; dry season; n = 10). Although samples from less than 10% of the season are extrapolated to the full season, such seasonality may be explained by the predominance of the southwest summer monsoon, which brings clean marine air masses to Mumbai. While heavy rains are an important contributor to aerosol removal during the monsoon season, meteorological data (relative humidity and T) suggest no heavy rains occurred during our sampling period. However, in winter, high levels of SOA and their day/night differences suggest significant contributions of continental aerosols through long-range transport together with local sources. The winter/summer pattern of SOA loadings was further supported by results from chemical transport models (NAQPMS and GEOS-Chem). Furthermore, our study suggests that monoterpene- and sesquiterpene-derived secondary organic carbon (SOC) were more significant than those of isoprene- and toluene-SOC at Mumbai.

Discovery and validation of blood biomarkers for suicidality.

Suicides are a leading cause of death in psychiatric patients, and in society at large. Developing more quantitative and objective ways (biomarkers) for predicting and tracking suicidal states would have immediate practical applications and positive societal implications. We undertook such an endeavor. First, building on our previous blood biomarker work in mood disorders and psychosis, we decided to identify blood gene expression biomarkers for suicidality, looking at differential expression of genes in the blood of subjects with a major mood disorder (bipolar disorder), a high-risk population prone to suicidality. We compared no suicidal ideation (SI) states and high SI states using a powerful intrasubject design, as well as an intersubject case-case design, to generate a list of differentially expressed genes. Second, we used a comprehensive Convergent Functional Genomics (CFG) approach to identify and prioritize from the list of differentially expressed gene biomarkers of relevance to suicidality. CFG integrates multiple independent lines of evidence-genetic and functional genomic data-as a Bayesian strategy for identifying and prioritizing findings, reducing the false-positives and false-negatives inherent in each individual approach. Third, we examined whether expression levels of the blood biomarkers identified by us in the live bipolar subject cohort are actually altered in the blood in an age-matched cohort of suicide completers collected from the coroner's office, and report that 13 out of the 41 top CFG scoring biomarkers (32%) show step-wise significant change from no SI to high SI states, and then to the suicide completers group. Six out of them (15%) remained significant after strict Bonferroni correction for multiple comparisons. Fourth, we show that the blood levels of SAT1 (spermidine/spermine N1-acetyltransferase 1), the top biomarker identified by us, at the time of testing for this study, differentiated future as well as past hospitalizations with suicidality, in a live cohort of bipolar disorder subjects, and exhibited a similar but weaker pattern in a live cohort of psychosis (schizophrenia/schizoaffective disorder) subjects. Three other (phosphatase and tensin homolog (PTEN), myristoylated alanine-rich protein kinase C substrate (MARCKS), and mitogen-activated protein kinase kinase kinase 3 (MAP3K3)) of the six biomarkers that survived Bonferroni correction showed similar but weaker effects. Taken together, the prospective and retrospective hospitalization data suggests SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but trait biomarkers as well. Fifth, we show how a multi-dimensional approach using SAT1 blood expression levels and two simple visual-analog scales for anxiety and mood enhances predictions of future hospitalizations for suicidality in the bipolar cohort (receiver-operating characteristic curve with area under the curve of 0.813). Of note, this simple approach does not directly ask about SI, which some individuals may deny or choose not to share with clinicians. Lastly, we conducted bioinformatic analyses to identify biological pathways, mechanisms and medication targets. Overall, suicidality may be underlined, at least in part, by biological mechanisms related to stress, inflammation and apoptosis.

Clinical Study and Management of Epistaxis.

Epistaxis is the most common emergency in otorhinolaryngology affecting up to 60% of the population in their lifetime. There are various local and systemic cause and includes both medical and surgical management. This study has been undertaken to study various etiopathogenesis and management of epistaxis. This is a prospective hospital-based study conducted on 100 patients of all age groups and both genders presenting with epistaxis to the Department of Otorhinolaryngology both on outpatient and inpatient basis. A detailed history taking with clinical examination is done. Data is entered in a structured performa, master chart prepared and is subjected to statistical analysis by SPSS software version 23. The most common age group was first decade (26%) followed by fourth decade (15%) with male (71%) predominance. Anterior epistaxis (87%) and bilateral nasal cavity involvement (65%) was predominantly seen. Most common causes for epistaxis are trauma (20%) followed by nasal infections (18%) and hypertension (17%). Majority of the patients underwent medical line of treatment (80%) followed by anterior nasal packing (12%), surgical intervention (7%), posterior nasal packing (1%). Epistaxis needs immediate restoration of hemodynamic parameters with first aid, airway assessment and control of bleeding. Majority of the cases were managed conservatively which is safe and cost effective method. Patients should be advised to avoid strenuous activity, nose picking and vigorous nose blowing. Severe recurrent epistaxis needed invasive interventions like nasal packing and blood transfusion.

Breast Cancer Diagnosis Using Virtualization and Extreme Learning Algorithm Based on Deep Feed Forward Networks.

One of the leading causes of death for women worldwide is breast cancer. Early detection and prompt treatment can reduce the risk of breast cancer-related death. Cloud computing and machine learning are crucial for disease diagnosis today, but they are especially important for those who live in distant places with poor access to healthcare. While machine learning-based diagnosis tools act as primary readers and aid radiologists in correctly diagnosing diseases, cloud-based technology can also assist remote diagnostics and telemedicine services. The promise of techniques based on Artificial Neural Networks (ANN) for sickness diagnosis has attracted the attention of several re-searchers. The 4 methods for the proposed research include preprocessing, feature extraction, and classification. A Smart Window Vestige Deletion (SWVD) technique is initially suggested for preprocessing. It consists of Savitzky-Golay (S-G) smoothing, updated 2-stage filtering, and adaptive time window division. This technique separates each channel into multiple time periods by adaptively pre-analyzing its specificity. On each window, an altered 2-stage filtering process is then used to retrieve some tumor information. After applying S-G smoothing and integrating the broken time sequences, the process is complete. In order to deliver effective feature extraction, the Deep Residual based Multiclass for architecture (DRMFA) is used. In histological photos, identify characteristics at the cellular and tissue levels in both tiny and large size patches. Finally, a fresh customized strategy that combines a better crow forage-ELM. Deep learning and the Extreme Learning Machine (ELM) are concepts that have been developed (ACF-ELM). When it comes to diagnosing ailments, the cloud-based ELM performs similarly to certain cutting-edge technology. The cloud-based ELM approach beats alternative solutions, according to the DDSM and INbreast dataset results. Significant experimental results show that the accuracy for data inputs is 0.9845, the precision is 0.96, the recall is 0.94, and the F1 score is 0.95.

Benzene: A critical review on measurement methodology, certified reference material, exposure limits with its impact on human health and mitigation strategies.

Benzene is a carcinogenic pollutant with significant emission sources present in the atmosphere. The need for accurate and precise measurement of benzene in the atmosphere has become increasingly evident due to its toxicity and the adverse health effects associated with exposure to different concentrations. Certified reference material (CRM) is essential to establish the traceability of measurement results. The present review compiles the available national and international measurement methods, certified reference materials (CRMs) for benzene and the limit of benzene in fuel composition (v/v) worldwide. Overall, the review indicates the benzene level in the atmosphere and the resulting impacts on the environment and human health, which frequently exceed the exposure limits of different environment regulatory agencies. An extensive literature review was conducted to gather information on monitoring and analysis methods for benzene, revealing that the most preferred method, i.e. Gas Chromatography- Flame Ionization Detector and Mass Spectrometry, is neither cost-effective nor suitable for real-time continuous monitoring. By analysing existing literature and studies, this review will shed light on the understanding of the importance of benzene pollution monitoring in ambient air and its implications for public health. Additionally, it will reflect the mitigation strategies applied by regulators & need for future revisions of air quality guidelines.

Exploring the hidden mental health consequences of malaria beyond the fever.

Malaria morbidity has various presentations and the focus now shifts to uncommon signs and symptoms of malaria infection such as cognitive impairment to address the morbidity when the mortality declines. About 50% of children admitted to hospitals due to malaria experience neurological complications due to factors like low blood sugar, inflammation, elevated pressure, decreased oxygen levels, and excitotoxicity. Malaria during pregnancy negatively also impacts children's cognitive, behavioral, and executive function leading to neurodevelopmental delay due to increased susceptibility which can significantly affect maternal and child health, leading to higher rates of underestimated factors like anxiety, depression, and PTSD. Despite having the world's second-largest tribal population, India's indigenous and tribal communities and their mental health are less explored and less understood. Western psychological tools and neurocognitive assessment tools are not universally applicable, thus necessitating the development of tailored tools to investigate psychological or neurocognitive impairment. This paper has illuminated the hidden mental health consequences of malaria infection, emphasizing the prevalence, nature, and implications of psychological distress among affected individuals. The findings underscore the importance of recognizing and addressing these psychological consequences in the holistic management and prevention of malaria and its mental health consequences.