Global marine phytoplankton dynamics analysis with machine learning and reanalyzed remote sensing.

Phytoplankton are the world's largest oxygen producers found in oceans, seas and large water bodies, which play crucial roles in the marine food chain. Unbalanced biogeochemical features like salinity, pH, minerals, etc., can retard their growth. With advancements in better hardware, the usage of Artificial Intelligence techniques is rapidly increasing for creating an intelligent decision-making system. Therefore, we attempt to overcome this gap by using supervised regressions on reanalysis data targeting global phytoplankton levels in global waters. The presented experiment proposes the applications of different supervised machine learning regression techniques such as random forest, extra trees, bagging and histogram-based gradient boosting regressor on reanalysis data obtained from the Copernicus Global Ocean Biogeochemistry Hindcast dataset. Results obtained from the experiment have predicted the phytoplankton levels with a coefficient of determination score (R2) of up to 0.96. After further validation with larger datasets, the model can be deployed in a production environment in an attempt to complement in-situ measurement efforts.

A Lung Cancer Patient Presenting With Gynecomastia: An Uncommon Paraneoplastic Syndrome.

Lung cancer is the most common neoplastic disorder associated with paraneoplastic syndromes. The most common paraneoplastic syndromes are the syndrome of inappropriate release of antidiuretic hormone (SIADH), hypercalcemia of malignancy, ectopic Cushing's syndrome, and various other neurological syndromes. A few case reports have reported gynecomastia as a paraneoplastic syndrome. Recognition of this uncommon presentation can aid in the early detection of associated malignancies, thus potentially improving outcomes. In this article, we are presenting the case of a male patient in his late sixties who, on presentation, had gynecomastia and was eventually diagnosed with non-small-cell lung cancer (NSCLC).

NMR and Mössbauer Studies Reveal a Temperature-Dependent Switch from S = 1 to 2 in a Nonheme Oxoiron(IV) Complex with Faster C-H Bond Cleavage Rates.

S = 2 FeIV═O centers generated in the active sites of nonheme iron oxygenases cleave substrate C-H bonds at rates significantly faster than most known synthetic FeIV═O complexes. Unlike the majority of the latter, which are S = 1 complexes, [FeIV(O)(tris(2-quinolylmethyl)amine)(MeCN)]2+ (3) is a rare example of a synthetic S = 2 FeIV═O complex that cleaves C-H bonds 1000-fold faster than the related [FeIV(O)(tris(pyridyl-2-methyl)amine)(MeCN)]2+ complex (0). To rationalize this significant difference, a systematic comparison of properties has been carried out on 0 and 3 as well as related complexes 1 and 2 with mixed pyridine (Py)/quinoline (Q) ligation. Interestingly, 2 with a 2-Q-1-Py donor combination cleaves C-H bonds at 233 K with rates approaching those of 3, even though Mössbauer analysis reveals 2 to be S = 1 at 4 K. At 233 K however, 2 becomes S = 2, as shown by its 1H NMR spectrum. These results demonstrate a unique temperature-dependent spin-state transition from triplet to quintet in oxoiron(IV) chemistry that gives rise to the high C-H bond cleaving reactivity observed for 2.

Comparison of Patient's Procedural Tolerance of EBUS-TBNA Performed Through Nasal Versus Oral Route: The NO-EBUS Randomized Clinical Trial.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a commonly performed procedure by the bronchoscopist for the evaluation of mediastinal lesions. However, evidence directly comparing the nasal and oral routes to guide the choice of an optimal insertion approach is scanty. METHODS: In this prospective, parallel-group, open-label randomized clinical trial, adults posted for a linear EBUS-TBNA examination under conscious sedation were randomized to undergo the procedure via the nasal or oral route. The primary objective was to assess the equivalence of subject-rated tolerance of EBUS-TBNA procedure in the 2 groups. Key secondary objectives were to assess the equivalence of subject-rated overall experience, willingness for a repeat procedure, operator-rated subject's tolerance, and operator-rated ease of performing the procedure. RESULTS: One hundred and eighty subjects were randomized in a 1:1 ratio to the nasal (n=98) or oral (n=82) group. Outcome measures were assessed by both per-protocol (PP) and intention-to-treat (ITT) analysis. Subject-rated procedural tolerance, overall satisfaction and operator's ease of performing the procedure were found to be equivalent in the 2 groups ( P <0.05 in all cases for PP and ITT analysis). The operator-rated subject's tolerance was, however, nonequivalent ( P =0.0596, 0.1286 for PP and ITT, respectively). Subject's willingness to undergo a repeat procedure was similar in both groups [90% CI of difference in proportions: (-0.023, 0.121) in PP and (-0.028, 0.115) in ITT analysis]. CONCLUSION: Nasal route for EBUS-TBNA could be considered where it is feasible and preferable for the patient as well as the operator.

Mesoscopic critical fluctuations.

We investigate the magnetic fluctuations in a mesoscopic critical region formed at the interface due to smooth time-independent spatial variations of a control parameter around its critical value. In the proximity of the spatial critical point, the order parameter fluctuations exhibit a mesoscopic nature, characterized by their significant size compared to the lattice constant, while gradually decaying away from the critical region. To explain this phenomenon, we present a minimal model that effectively captures this behavior and demonstrates its connection to the integrable Painlevé-II equation governing the local order parameter. By leveraging the well-established mathematical properties of this equation, we gain valuable insights into the nonlinear susceptibilities exhibited within this region.

Predictors of Poor Outcome in Patients with COVID-19 associated Respiratory Failure: A Retrospective Observational Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is majorly known to cause mild to moderate disease, but a small fraction of patients may develop respiratory failure due to diffuse lung injury, requiring management in the intensive care unit (ICU). This study attempts to identify factors that can predict unfavorable outcomes in moderate to severe COVID-19 patients. METHODS: Hospital records of 120 COVID-19 patients admitted to the ICU were retrospectively analyzed and data pertaining to demographic, clinical, and laboratory parameters were obtained. These data were then compared with outcome parameters like survival, duration of hospital stay, and various adverse events. RESULTS: Out of 120 patients, 70% were male, with a mean age of 54.44 years [standard deviation (SD) ± 14.24 years]. Presenting symptoms included breathlessness (100%), cough (94.17%), fever (82.5%), and sore throat (10.83%). Diabetes, hypertension, and chronic obstructive pulmonary disease (COPD) were the common comorbidities associated. Increased serum D-dimer, ferritin, interleukin-6 (IL-6) levels, and unvaccinated status were associated with higher mortality. Overall, 25.83% of patients survived, 24.41% of patients developed septic shock, and 10.6% of patients were discharged on oxygen. World Health Organization (WHO) clinical progression scale score ≥ 6 had 57 and 82% sensitivity and 83 and 77% specificity on days 7 and 14 after admission, respectively, for predicting mortality. A baseline National Early Warning Score 2 (NEWS 2) ≥ 9 had 48% sensitivity and 88% specificity for predicting mortality. CONCLUSION: Advanced age and associated comorbidities are linked to adverse outcomes in moderate to severe COVID-19. Persistently high D-dimer levels, despite standard treatment, may also contribute to increased mortality. WHO clinical progression scale and NEWS 2 have high specificity for predicting mortality.

Clinical Profile, Risk Factors, and Therapeutic Outcome of Cavitating Fungal Pneumonia Coinfection in COVID-19 Patients: A Retrospective Analysis.

BACKGROUND: An end to the novel coronavirus disease 2019 (COVID-19) pandemic appears to be a distant dream. To make matters worse, there has been an alarming upsurge in the incidence of cavitating invasive fungal pneumonia associated with COVID-19, reported from various parts of the world including India. Therefore, it remains important to identify the clinical profile, risk factors, and outcome of this group of patients. METHODS: Out of 50 moderate to severe COVID-19 inpatients with thoracic computed tomographic (CT) evidence of lung cavitation, we retrospectively collected demographic and clinical data of those diagnosed with fungal pneumonia for further investigation. We determined the association between risk factors related to 30-day and 60-day mortality. RESULTS: Of the 50 COVID-19 patients with cavitating lung lesions, 22 (44 %) were identified to have fungal pneumonia. Most of these patients (n = 16, 72.7 %) were male, with a median (range) age of 56 (38-64) years. On chest CT imaging, the most frequent findings were multiple cavities (n = 13, 59.1 %) and consolidation (n = 14, 63.6 %). Mucormycosis (n = 10, 45.5 %) followed by Aspergillus fumigatus (n = 9, 40.9 %) were the common fungi identified. 30-day and 60-day mortalities were seen in 12 (54.5 %) and 16 (72.7 %) patients, respectively. On subgroup analysis, high cumulative prednisolone dose was an independent risk factor associated with 30-day mortality (p = 0.024). CONCLUSION: High cumulative prednisolone dose, baseline neutropenia, hypoalbuminemia, multiple cavities on CT chest, leukopenia, lymphopenia and raised inflammatory markers were associated with poor prognosis in severe COVID-19 patients with cavitating fungal pneumonia.

Flexible battery-less wireless glucose monitoring system.

In this work, a low power microcontroller-based near field communication (NFC) interfaced with a flexible abiotic glucose hybrid fuel cell is designed to function as a battery-less glucose sensor. The abiotic glucose fuel cell is fabricated by depositing colloidal platinum (co-Pt) on the anodic region and silver oxide nanoparticles-multiwalled carbon nanotubes (Ag2O-MWCNTs) composite on the cathodic region. The electrochemical behavior is characterized using cyclic voltammetry and chronoamperometry. This glucose hybrid fuel cell generated an open circuit voltage of 0.46 V, short circuit current density of 0.444 mA/cm2, and maximum power density of 0.062 mW/cm2 at 0.26 V in the presence of 7 mM physiologic glucose. Upon device integration of the abiotic glucose hybrid fuel cell with the NFC module, the data from the glucose monitoring system is successfully transmitted to an android application for visualization at the user interface. The cell voltage correlated (r2 = 0.989) with glucose concentration (up to 19 mM) with a sensitivity of 13.9 mV/mM•cm2.

Comparative Effectiveness and Safety of Methotrexate Versus PUVA in Severe Chronic Stable Plaque Psoriasis.

BACKGROUND: Psoriasis is a chronic, inflammatory, immune-mediated, debilitating skin disease affecting approximately 2%-3% of the global population. Various treatment modalities are available for extensive psoriasis which include methotrexate, cyclosporine, retinoids, oral PUVA therapy, and biologic agents. AIMS AND OBJECTIVES: The aim of this study was to compare the effectiveness and safety of methotrexate vs. PUVA in severe chronic plaque psoriasis with BSA >20%. MATERIALS AND METHODS: A randomized open-label clinical study was performed. Sixty patients with extensive stable plaque psoriasis were recruited in the study. Thirty patients received methotrexate at a dose of 0.4 mg/kg up to a maximum of 15 mg/week and the rest 30 were treated by PUVA, 8-methoxy psoralen tablet (20 mg) followed by UVA started at the dose of 1 j/cm2 thrice weekly with an increment of 20% dose every third sitting until 2.5 j/cm2 is reached. Both forms of treatment were continued for 10 weeks or until PASI 90 achieved, which-ever was earlier. Clinical examination, blood investigation, PASI scoring, and photograph were repeated in serial intervals during the study. At the end of study, the data were compiled, tabulated, and analyzed. RESULT: In the PUVA group, 90% achieved PASI-50 and 63.33% achieved PASI-90, in the methotrexate group all patients achieved both PASI-50 and PASI-90. Methotrexate acted significantly faster than PUVA in disease clearance. In the methotrexate group decreased platelet count in 13.33% patients, decreased hemoglobin (<10 gm/dl), elevated liver enzyme, each of these developed in 10% of patients. In the PUVA group, no serious side effects were observed. CONCLUSIONS: Methotrexate is more efficacious with lesser incidence of subjective complications and more incidence of laboratory complications compared to PUVA in extensive plaque psoriasis.

Tejaas: reverse regression increases power for detecting trans-eQTLs.

Trans-acting expression quantitative trait loci (trans-eQTLs) account for ≥70% expression heritability and could therefore facilitate uncovering mechanisms underlying the origination of complex diseases. Identifying trans-eQTLs is challenging because of small effect sizes, tissue specificity, and a severe multiple-testing burden. Tejaas predicts trans-eQTLs by performing L2-regularized "reverse" multiple regression of each SNP on all genes, aggregating evidence from many small trans-effects while being unaffected by the strong expression correlations. Combined with a novel unsupervised k-nearest neighbor method to remove confounders, Tejaas predicts 18851 unique trans-eQTLs across 49 tissues from GTEx. They are enriched in open chromatin, enhancers, and other regulatory regions. Many overlap with disease-associated SNPs, pointing to tissue-specific transcriptional regulation mechanisms.

Dysregulated RASGRP1 expression through RUNX1 mediated transcription promotes autoimmunity.

RasGRP1 is a Ras guanine nucleotide exchange factor, and an essential regulator of lymphocyte receptor signaling. In mice, Rasgrp1 deletion results in defective T lymphocyte development. RASGRP1-deficient patients suffer from immune deficiency, and the RASGRP1 gene has been linked to autoimmunity. However, how RasGRP1 levels are regulated, and if RasGRP1 dosage alterations contribute to autoimmunity remains unknown. We demonstrate that diminished Rasgrp1 expression caused defective T lymphocyte selection in C57BL/6 mice, and that the severity of inflammatory disease inversely correlates with Rasgrp1 expression levels. In patients with autoimmunity, active inflammation correlated with decreased RASGRP1 levels in CD4+ T cells. By analyzing H3K27 acetylation profiles in human T cells, we identified a RASGRP1 enhancer that harbors autoimmunity-associated SNPs. CRISPR-Cas9 disruption of this enhancer caused lower RasGRP1 expression, and decreased binding of RUNX1 and CBFB transcription factors. Analyzing patients with autoimmunity, we detected reduced RUNX1 expression in CD4+ T cells. Lastly, we mechanistically link RUNX1 to transcriptional regulation of RASGRP1 to reveal a key circuit regulating RasGRP1 expression, which is vital to prevent inflammatory disease.

Mitochondria control mTORC1 activity-linked compartmentalization of eIF4E to regulate extracellular export of microRNAs.

Defective intracellular trafficking and export of microRNAs (miRNAs) have been observed in growth-retarded mammalian cells having impaired mitochondrial potential and dynamics. Here, we found that uncoupling protein 2 (Ucp2)-mediated depolarization of mitochondrial membrane also results in progressive sequestration of miRNAs within polysomes and lowers their release via extracellular vesicles. Interestingly, the impaired miRNA-trafficking process in growth-retarded human cells could be reversed in the presence of Genipin, an inhibitor of Ucp2. Mitochondrial detethering of endoplasmic reticulum (ER), observed in cells with depolarized mitochondria, was found to be responsible for defective compartmentalization of translation initiation factor eIF4E to polysomes attached to ER. This caused a retarded translation process accompanied by enhanced retention of miRNAs and target mRNAs within ER-attached polysomes to restrict extracellular export of miRNAs. Reduced compartment-specific activity of the mammalian target of rapamycin complex 1 (mTORC1), the master regulator of protein synthesis, in cells with defective mitochondria or detethered ER, caused reduced phosphorylation of eIF4E-BP1 and prevented eIF4E targeting to ER-attached polysomes and miRNA export. These data suggest how mitochondrial membrane potential and dynamics, by affecting mTORC1 activity and compartmentalization, determine the subcellular localization and export of miRNAs.

Electrochemical Detection of Neurotransmitters.

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer's, Parkinson's, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the complex intercommunication of neurotransmitters. Therefore, it is crucial to develop clinical assessment techniques that are sensitive and reliable to monitor and modulate these chemical messengers and screen diseases. This review focuses on summarizing the current electrochemical measurement techniques that are capable of sensing neurotransmitters with high temporal resolution in real time. Advanced neurotransmitter sensing platforms that integrate nanomaterials and biorecognition elements are explored.

Sc3+-Promoted O-O Bond Cleavage of a (µ-1,2-Peroxo)diiron(III) Species Formed from an Iron(II) Precursor and O2 to Generate a Complex with an FeIV2(µ-O)2 Core.

Soluble methane monooxygenase (sMMO) carries out methane oxidation at 4 °C and under ambient pressure in a catalytic cycle involving the formation of a peroxodiiron(III) intermediate (P) from the oxygenation of the diiron(II) enzyme and its subsequent conversion to Q, the diiron(IV) oxidant that hydroxylates methane. Synthetic diiron(IV) complexes that can serve as models for Q are rare and have not been generated by a reaction sequence analogous to that of sMMO. In this work, we show that [FeII(Me3NTB)(CH3CN)](CF3SO3)2 (Me3NTB = tris((1-methyl-1H-benzo[d]imidazol-2-yl)methyl)amine) (1) reacts with O2 in the presence of base, generating a (µ-1,2-peroxo)diiron(III) adduct with a low O-O stretching frequency of 825 cm-1 and a short Fe···Fe distance of 3.07 Å. Even more interesting is the observation that the peroxodiiron(III) complex undergoes O-O bond cleavage upon treatment with the Lewis acid Sc3+ and transforms into a bis(µ-oxo)diiron(IV) complex, thus providing a synthetic precedent for the analogous conversion of P to Q in the catalytic cycle of sMMO.

Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases.

Raf kinases are important cancer drug targets. Paradoxically, many B-Raf inhibitors induce the activation of Raf kinases. Cryo-electron microscopy structural analysis of a phosphorylated B-Raf kinase domain dimer in complex with dimeric 14-3-3, at a resolution of ~3.9 angstroms, shows an asymmetric arrangement in which one kinase is in a canonical "active" conformation. The distal segment of the C-terminal tail of this kinase interacts with, and blocks, the active site of the cognate kinase in this asymmetric arrangement. Deletion of the C-terminal segment reduces Raf activity. The unexpected asymmetric quaternary architecture illustrates how the paradoxical activation of Raf by kinase inhibitors reflects an innate mechanism, with 14-3-3 facilitating inhibition of one kinase while maintaining activity of the other. Conformational modulation of these contacts may provide new opportunities for Raf inhibitor development.

Spectroscopic and Reactivity Comparisons between Nonheme Oxoiron(IV) and Oxoiron(V) Species Bearing the Same Ancillary Ligand.

This work directly compares the spectroscopic and reactivity properties of an oxoiron(IV) and an oxoiron(V) complex that are supported by the same neutral tetradentate N-based PyNMe3 ligand. A complete spectroscopic characterization of the oxoiron(IV) species (2) reveals that this compound exists as a mixture of two isomers. The reactivity of the thermodynamically more stable oxoiron(IV) isomer (2b) is directly compared to that exhibited by the previously reported 1e--oxidized analogue [FeV(O)(OAc)(PyNMe3)]2+ (3). Our data indicates that 2b is 4 to 5 orders of magnitude slower than 3 in hydrogen atom transfer (HAT) from C-H bonds. The origin of this huge difference lies in the strength of the O-H bond formed after HAT by the oxoiron unit, the O-H bond derived from 3 being about 20 kcal·mol-1 stronger than that from 2b. The estimated bond strength of the FeIVO-H bond of 100 kcal·mol-1 is very close to the reported values for highly active synthetic models of compound I of cytochrome P450. In addition, this comparative study provides direct experimental evidence that the lifetime of the carbon-centered radical that forms after the initial HAT by the high valent oxoiron complex depends on the oxidation state of the nascent Fe-OH complex. Complex 2b generates long-lived carbon-centered radicals that freely diffuse in solution, while 3 generates short-lived caged radicals that rapidly form product C-OH bonds, so only 3 engages in stereoretentive hydroxylation reactions. Thus, the oxidation state of the iron center modulates not only the rate of HAT but also the rate of ligand rebound.

NMR Reveals That a Highly Reactive Nonheme FeIV =O Complex Retains Its Six-Coordinate Geometry and S=1 State in Solution.

The [FeIV (O)(Me3 NTB)]2+ (Me3 NTB=tris[(1-methyl-benzimidazol-2-yl)methyl]amine) complex 1 has been shown by Mössbauer spectroscopy to have an S=1 ground state at 4 K, but is proposed to become an S=2 trigonal-bipyramidal species at higher temperatures based on a DFT model to rationalize its very high C-H bond-cleavage reactivity. In this work, 1 H NMR spectroscopy was used to determine that 1 does not have C3 -symmetry in solution and is not an S=2 species. Our results show that 1 is unique among nonheme FeIV =O complexes in retaining its S=1 spin state and high reactivity at 193 K, providing evidence that S=1 FeIV =O complexes can be as reactive as their S=2 counterparts. This result emphasizes the need to identify factors besides the ground spin state of the FeIV =O center to rationalize nonheme oxoiron(IV) reactivity.

Disease awareness advertising (DAA) in emerging economy: A comparison between views of consumers and pharmaceutical professionals.

Research on effectiveness of DAA is limited. Existing researches explore impact of DAA only on relationship between drug manufacturers and consumers. However, in reality, pharma marketing revolves around three major stakeholders: the pharmaceutical companies, physicians and consumers. Pharmaceutical professionals on behalf of drug manufacturers have last mile connectivity with end users and they are an important stakeholder in this entire marketing relationship network. So, it is important for marketers to capture views of pharma professionals in addition to physicians and consumers. The current research evaluates views of consumers and pharmaceutical professionals about effectiveness of unbranded DAA for product message communication.