Simultaneous inhibition of two neutrophil serine proteases by the S. aureus innate immune evasion protein EapH2.

Extracellular adherence protein domain (EAP) proteins are high-affinity, selective inhibitors of neutrophil serine proteases (NSP), including cathepsin-G (CG) and neutrophil elastase (NE). Most Staphylococcus aureus isolates encode for two EAPs, EapH1 and EapH2, that contain a single functional domain and share 43% identity with one another. Although structure/function investigations from our group have shown that EapH1 uses a globally similar binding mode to inhibit CG and NE, NSP inhibition by EapH2 is incompletely understood due to a lack of NSP/EapH2 cocrystal structures. To address this limitation, we further studied NSP inhibition by EapH2 in comparison with EapH1. Like its effects on NE, we found that EapH2 is a reversible, time-dependent, and low nanomolar affinity inhibitor of CG. We characterized an EapH2 mutant which suggested that the CG binding mode of EapH2 is comparable to EapH1. To test this directly, we used NMR chemical shift perturbation to study EapH1 and EapH2 binding to CG and NE in solution. Although we found that overlapping regions of EapH1 and EapH2 were involved in CG binding, we found that altogether distinct regions of EapH1 and EapH2 experienced changes upon binding to NE. An important implication of this observation is that EapH2 might be capable of binding and inhibiting CG and NE simultaneously. We confirmed this unexpected feature by solving crystal structures of the CG/EapH2/NE complex and demonstrating their functional relevance through enzyme inhibition assays. Together, our work defines a new mechanism of simultaneous inhibition of two serine proteases by a single EAP protein.

Impact of the COVID-19 pandemic on treatment of patients with acute myeloid leukaemia in India.

During the COVID-19 pandemic, our findings highlight changes in AML management strategies in India. There was a decrease in overall patient registrations, particularly at large referral centers, while smaller centers saw an increase, reflecting a shift towards more localized care. This shift was accompanied by a rise in the use of hypomethylating agents (HMAs). Despite these changes, survival outcomes remained comparable to pre-pandemic levels, likely due to improved infection control measures and maintaining treatment protocols. Our study concludes that standard AML care remained feasible during the pandemic, emphasizing the importance of continuing treatment for eligible patients even in times of crisis.

Staphylococcal peroxidase inhibitor (SPIN): Investigation of the inhibitory N-terminal domain via a stabilizing disulfide insertion.

Staphylococcus aureus secretes an array of small proteins that inhibit key enzyme-catalyzed reactions necessary for proper function of the human innate immune system. Among these, the Staphylococcal Peroxidase Inhibitor, SPIN, blocks the activity of myeloperoxidase (MPO) and thereby disrupts the HOCl-generating system of neutrophils. Previous studies on S. aureus SPIN have shown that it relies on a C-terminal α-helical bundle domain to mediate initial binding to MPO, but requires a disordered N-terminal region to fold into a ß-hairpin conformation to inhibit MPO activity. To further investigate the structure/function relationship of SPIN, we introduced two cysteine residues into its N-terminal region to trap SPIN in its MPO-bound conformation and characterized the modified protein, which we refer to here as SPIN-CYS. Although control experiments confirmed the presence of the disulfide bond in SPIN-CYS, solution structure determination revealed that the N-terminal region of SPIN-CYS adopted a physically constrained series of lariat-like structures rather than a well-defined ß-hairpin. Nevertheless, SPIN-CYS exhibited a gain in inhibitory potency against human MPO when compared to wild-type SPIN. This gain of function persisted even in the presence of deleterious mutations within the C-terminal α-helical bundle domain. Surface plasmon resonance studies showed that the gain in potency arose through an increase in apparent affinity of SPIN-CYS for MPO, which was driven primarily by an increased association rate with MPO when compared to wild-type SPIN. Together, this work provides new information on the coupled binding and folding events required to manifest biological activity of this unusual MPO inhibitor.

New advances in understanding inhibition of myeloperoxidase and neutrophil serine proteases by two families of staphylococcal innate immune evasion proteins.

Neutrophils are the most abundant leukocytes in humans and play an important early role in the innate immune response against microorganisms. Neutrophil phagosomes contain high concentrations of antibacterial enzymes, including myeloperoxidase (MPO) and the neutrophil serine proteases (NSPs). These antibacterial enzymes can also be released extracellularly upon degranulation or as a component of neutrophil extracellular traps (NETs). Due to host/pathogen coevolution, S. aureus expresses a diverse arsenal of innate immune evasion proteins that target many aspects of the neutrophil antibacterial response. In the last decade, two new classes of staphylococcal innate immune evasion proteins that act as potent, selective inhibitors of MPO and NSPs, respectively, have been discovered. The Staphylococcal Peroxidase INhibitor (SPIN) is a small ∼8.3 kDa α-helical bundle protein that blocks MPO activity by interfering with substrate and product exchange with the MPO active site. The Extracellular Adherence Protein (EAP) family consists of three unique proteins comprised of one or more copies of an ∼11 kDa ß-grasp domain capable of high-affinity, selective, non-covalent inhibition of NSPs. This brief review article summarizes recent advances in understanding the structural and functional properties of SPIN and EAP family members and outlines some potential avenues for future investigation of these enzyme inhibitors.

Treatment challenges and outcomes of older patients with acute myeloid leukemia from India.

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

Tailoring the Photophysical Properties of a Homoleptic Iron(II) Tetra N-Heterocyclic Carbene Complex by Attaching an Imidazolium Group to the (C∧N∧C) Pincer Ligand─A Comparative Study.

We here report the synthesis of the homoleptic iron(II) N-heterocyclic carbene (NHC) complex [Fe(miHpbmi)2](PF6)4 (miHpbmi = 4-((3-methyl-1H-imidazolium-1-yl)pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) and its electrochemical and photophysical properties. The introduction of the π-electron-withdrawing 3-methyl-1H-imidazol-3-ium-1-yl group into the NHC ligand framework resulted in stabilization of the metal-to-ligand charge transfer (MLCT) state and destabilization of the metal-centered (MC) states. This resulted in an improved excited-state lifetime of 16 ps compared to the 9 ps for the unsubstituted parent compound [Fe(pbmi)2](PF6)2 (pbmi = (pyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)) as well as a stronger MLCT absorption band extending more toward the red spectral region. However, compared to the carboxylic acid derivative [Fe(cpbmi)2](PF6)2 (cpbmi = 1,1'-(4-carboxypyridine-2,6-diyl)bis(3-methylimidazol-2-ylidene)), the excited-state lifetime of [Fe(miHpbmi)2](PF6)4 is the same, but both the extinction and the red shift are more pronounced for the former. Hence, this makes [Fe(miHpbmi)2](PF6)4 a promising pH-insensitive analogue of [Fe(cpbmi)2](PF6)2. Finally, the excited-state dynamics of the title compound [Fe(miHpbmi)2](PF6)4 was investigated in solvents with different viscosities, however, showing very little dependency of the depopulation of the excited states on the properties of the solvent used.

How Rigidity and Conjugation of Bidentate Ligands Affect the Geometry and Photophysics of Iron N-Heterocyclic Complexes: A Comparative Study.

Two iron complexes featuring the bidentate, nonconjugated N-heterocyclic carbene (NHC) 1,1'-methylenebis(3-methylimidazol-2-ylidene) (mbmi) ligand, where the two NHC moieties are separated by a methylene bridge, have been synthesized to exploit the combined influence of geometric and electronic effects on the ground- and excited-state properties of homoleptic FeIII-hexa-NHC [Fe(mbmi)3](PF6)3 and heteroleptic FeII-tetra-NHC [Fe(mbmi)2(bpy)](PF6)2 (bpy = 2,2'-bipyridine) complexes. They are compared to the reported FeIII-hexa-NHC [Fe(btz)3](PF6)3 and FeII-tetra-NHC [Fe(btz)2(bpy)](PF6)2 complexes containing the conjugated, bidentate mesoionic NHC ligand 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene) (btz). The observed geometries of [Fe(mbmi)3](PF6)3 and [Fe(mbmi)2(bpy)](PF6)2 are evaluated through L-Fe-L bond angles and ligand planarity and compared to those of [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The FeII/FeIII redox couples of [Fe(mbmi)3](PF6)3 (-0.38 V) and [Fe(mbmi)2(bpy)](PF6)2 (-0.057 V, both vs Fc+/0) are less reducing than [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. The two complexes show intense absorption bands in the visible region: [Fe(mbmi)3](PF6)3 at 502 nm (ligand-to-metal charge transfer, 2LMCT) and [Fe(mbmi)2(bpy)](PF6)2 at 410 and 616 nm (metal-to-ligand charge transfer, 3MLCT). Lifetimes of 57.3 ps (2LMCT) for [Fe(mbmi)3](PF6)3 and 7.6 ps (3MLCT) for [Fe(mbmi)2(bpy)](PF6)2 were probed and are somewhat shorter than those for [Fe(btz)3](PF6)3 and [Fe(btz)2(bpy)](PF6)2. [Fe(mbmi)3](PF6)3 exhibits photoluminescence at 686 nm (2LMCT) in acetonitrile at room temperature with a quantum yield of (1.2 ± 0.1) × 10-4, compared to (3 ± 0.5) × 10-4 for [Fe(btz)3](PF6)3.

Using Iron L-Edge and Nitrogen K-Edge X-ray Absorption Spectroscopy to Improve the Understanding of the Electronic Structure of Iron Carbene Complexes.

Iron-centered N-heterocyclic carbene compounds have attracted much attention in recent years due to their long-lived excited states with charge transfer (CT) character. Understanding the orbital interactions between the metal and ligand orbitals is of great importance for the rational tuning of the transition metal compound properties, e.g., for future photovoltaic and photocatalytic applications. Here, we investigate a series of iron-centered N-heterocyclic carbene complexes with +2, + 3, and +4 oxidation states of the central iron ion using iron L-edge and nitrogen K-edge X-ray absorption spectroscopy (XAS). The experimental Fe L-edge XAS data were simulated and interpreted through restricted-active space (RAS) and multiplet calculations. The experimental N K-edge XAS is simulated and compared with time-dependent density functional theory (TDDFT) calculations. Through the combination of the complementary Fe L-edge and N K-edge XAS, direct probing of the complex interplay of the metal and ligand character orbitals was possible. The σ-donating and π-accepting capabilities of different ligands are compared, evaluated, and discussed. The results show how X-ray spectroscopy, together with advanced modeling, can be a powerful tool for understanding the complex interplay of metal and ligand.

Surgical Cholecystectomy Score (SCS) for grading the difficulty of laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is the standard of care for symptomatic gall stone disease. A good scoring system is necessary to standardize the reporting. Our aim was to develop and validate an objective scoring system, the Surgical Cholecystectomy Score (SCS) to grade the difficulty of LC. METHODS: The study was conducted in a single surgical unit at a tertiary care hospital in two phases from January 2017 to April 2021. Retrospective data was analysed and the difficulty of each procedure was graded according to the modified Nassar's scoring system. Significant preoperative and intraoperative data obtained was given a weightage score. In phase II, these scores were validated on a prospective cohort. Each procedure was classified either as easy, moderately difficult or difficult. STATISTICAL ANALYSIS: A univariate analysis was performed on the data followed by a multivariate regression analysis. Bidirectional stepwise selection was done to select the most significant variables. The Beta /Schneeweiss scoring system was used to generate a rounded risk score. RESULTS: Data of 800 patients was retrieved and graded. 10 intraoperative parameters were found to be significant. Each variable was assigned a rounded risk score. The final SCS range for intraoperative parameters was 0-15. The scoring system was validated on a cohort of 249 LC. In the final scoring, cut off SCS of > 8 was found to correlate with difficult procedures. Score of < 2 was equivalent to easy LC. A score between 2 and 8 indicated moderate difficulty. The area under ROC curve was 0.98 and 0.92 for the intraoperative score indicating that the score was an excellent measure of the difficulty level of LCs. CONCLUSION: The scoring system developed in this study has shown an excellent correlation with the difficulty of LC. It needs to be validated in different cohorts and across multiple centers further.

High-frequency stock market order transitions during the US-China trade war 2018: A discrete-time Markov chain analysis.

Statistical analysis of high-frequency stock market order transaction data is conducted to understand order transition dynamics. We employ a first-order time-homogeneous discrete-time Markov chain model to the sequence of orders of stocks belonging to six different sectors during the US-China trade war of 2018. The Markov property of the order sequence is validated by the Chi-square test. We estimate the transition probability matrix of the sequence using maximum likelihood estimation. From the heatmap of these matrices, we found the presence of active participation by different types of traders during high volatility days. On such days, these traders place limit orders primarily with the intention of deleting the majority of them to influence the market. These findings are supported by high stationary distribution and low mean recurrence values of add and delete orders. Further, we found similar spectral gap and entropy rate values, which indicates that similar trading strategies are employed on both high and low volatility days during the trade war. Among all the sectors considered in this study, we observe that there is a recurring pattern of full execution orders in the Finance & Banking sector. This shows that the banking stocks are resilient during the trade war. Hence, this study may be useful in understanding stock market order dynamics and devise trading strategies accordingly on high and low volatility days during extreme macroeconomic events.

Harnessing the Phytochemistry Through Pesticidal Potential of Diverse Elsholtzia Species: A Path to Sustainable Agriculture.

This study investigates the phytochemical profiles and pesticidal activities of various Elsholtzia species, including E. ciliata, E. flava, E. fruticosa, and E. eriostachya, to discover their bioactive potential for sustainable pest management. Through comparative phytochemical analysis using GC-MS technique, key compounds in the essential oils were identified. The major components were thymoquinone (44.97%) in E. ciliata, shisofuran (28.66%) in E. flava, perillene (50.88%) in E. fruticosa, and pinocarvone (42.41%) in E. eriostachya. Despite variability in chemical composition, all species primarily contained oxygenated monoterpenes. The bioactivity of the oils was evaluated for their nematicidal and herbicidal bioassays. E. ciliata showed the highest egg hatching inhibition and juvenile mortality of M. incognita, while E. flava exhibited the lowest activity. For herbicidal activity, E. eriostachya achieved 96.70% seed germination inhibition, 100% root growth inhibition, and 95.56% shoot growth inhibition. E. flava showed the lowest inhibition in germination, root length, and shoot length at 66.70%, 81.56%, and 85.28%, respectively. The findings revealed significant variations in phytochemical composition and pesticidal efficacy, emphasizing the importance of species selection for pest management. This research highlights the bioactive potential of Elsholtzia species in sustainable pest management strategies.

Seasonal Study Chemical Profiles and Bioactivities of Hedychium coronarium J. Koenig Essential Oils: Nematicidal, Insecticidal, Phytotoxic, Antifungal Potentials, and Molecular Docking Insights.

Hedychium coronarium plant has attracted considerable attention from researchers due to its diverse phytochemical composition and potential therapeutic applications. The objective of this study was to evaluate the phytochemical profile and biological attributes of H. coronarium essential oils collected during different seasons in the Kumaun region of Uttarakhand. The essential oils were extracted from the rhizomes using hydrodistillation with a Clevenger-type apparatus yielding between 0.07% to 0.38% (w/w). The major compounds identified by GC-MS analysis exhibited seasonal variations and included 1,8-cineole (26.6-38.5%), coronarin E (11.9-18.8%), α-pinene (5.00-14.9%), α-terpineol (4.2-9.3%), (E)-ß-caryophyllene (1.2-9.7%), and linalool (0.4-2.9%). To illustrate the variations in oil composition, visualization techniques such as heat map and PCA were employed. The essential oils demonstrated potential biological activity in all tests conducted. The molecular modeling study indicated that the potential mechanism may be associated with acetylcholinesterase. Consequently, this study contributes to the development of novel natural pesticides.

Circulating serotypes and genotypes of dengue virus in North India: An observational study.

BACKGROUND OBJECTIVES: This study reports observation on circulating serotypes and genotypes of Dengue Virus in North India. METHODS: Serum samples were obtained from suspected cases of dengue referred to the virus diagnostic laboratory during 2014 to 2022. All samples were tested for anti-dengue virus IgM antibodies and NS1Ag by ELISA. NS1Ag positive samples were processed for serotyping and genotyping. RESULTS: Total 41,476 dengue suspected cases were referred to the laboratory of which 12,292 (29.6%) tested positive. Anti-Dengue Virus IgM antibodies, NS1Ag, both IgM and NS1Ag, were positive in 7007 (57.4%); 3200 (26.0%) and 2085 (16.0%) cases respectively. Total 762 strains were serotyped during 9-year period. DENV-1, DENV-2, DENV-3 and DENV-4 serotypes were found in 79 (10.37%), 506 (66.40%), 151 (19.82%) and 26 (3.41%) cases respectively. DENV-1, DENV-2 and DENV-3 were in circulation throughout. Total 105 strains were genotyped. Genotype IV of DENV-1 serotype was circulating till 2014 which was later replaced by genotype V. A distinct seasonality with increase in number of cases in post-monsoon period was seen. INTERPRETATION CONCLUSION: DENV-1, DENV-2 and DENV-3 were found to be in circulation in North India. Predominant serotype/genotype changed at times, but not at regular intervals.

Giant Cell Tumor of the Tendon Sheath of the Hand: Analysis of Factors Impacting Recurrence.

Background Giant cell tumors of the tendon sheath (GCTTS) of the hand are considered the second most common benign tumors of the hand after ganglion cysts. Excision biopsy is considered the standard treatment at present. They are notorious for having a very high rate of recurrence as given in many studies. Many factors are said to be associated with recurrence of the tumors. The goal of this study is to evaluate the long-term results of a series of 48 patients operated on at a single institute and to find out if there is any correlation between the proposed risk factors with recurrence. Methods A retrospective analysis was done in cases of GCTTS operated on between 2015 and 2021. The patients were invited for follow-up for a minimum of 2 years, and the patient files were reviewed. Further data were collected at follow-up including recurrence, range of movement, sensation, skin necrosis, scarring, and digital neuropathy. A data analysis was done. The correlation between the proposed risk factors and recurrence was calculated with the Pearson correlation coefficient. A p -value of less than 0.05 was considered statistically significant. Results During the 6 years, 48 patients were operated on. Recurrence was observed in eight patients (16%) at an average of 38.7 months from the time of surgery. Of the risk factors, tumors with satellite nodules and tumor adjacency to joint correlated significantly with recurrence. No complications were observed during follow-up. Conclusion GCTTS of the hand has a high propensity to recur. The presence of satellite nodules and proximity to interphalangeal joints are two important risk factors for recurrence. Magnification during surgery ensures complete excision of the tumor and reduces the chance of recurrence.

Utility of Fat Grafting in Chronic Wounds.

Introduction The history of wounds dates back to the evolution of mankind. Throughout the centuries, management modalities of wounds have undergone drastic changes. With the advent of technology, we have multiple options for wound care, but none of them can be called the gold standard of wound care. Autologous fat grafting (AFG) is one of the most routinely performed procedures in aesthetic surgery. Fat grafting has shown beneficial effects in the healing of wounds. The regenerative potential of autologous fat is contributed by the adipose-derived stem cells present within the stromal vascular fraction, which are capable of differentiating into multiple cell types. This study aims to analyze the usefulness of AFG in cutaneous wound healing. Materials and Methods This prospective, study was conducted in our institute between April 2021 and May 2023. Eighteen patients with nonhealing wounds were included in the study. For assessing wound healing all the patients were first managed with conventional dressing for 2 weeks before surgery. After routine preoperative workup, the procedure was performed under local anesthesia in most cases. Fat was harvested from the lower abdomen and after emulsification, was injected into the edge and floor of the ulcer. The dressing was changed on the third postoperative day and the outcome was assessed. Results Eighteen patients (M:F ratio 8:1), with a mean age of 35.61 ± 12. 64 years (range 10-65 years), were included in this study. The most common etiology was trauma (44%), others being postop infection (17%), veno-lymphatic ulcer (17%), burns (11%), insect bite (5%), and trophic ulcer (5%). Majority of the wounds (95%) healed without the need for any extra intervention. The mean period taken for complete wound healing was 5.05 weeks. Conclusion Complete wound healing was achieved in majority of the patients without any complications. We recommend the usage of AFG for nonhealing wounds, as the procedure is relatively simple and can be performed after basic training. Larger-scale randomized controlled trials should be conducted to prove their efficacy in the management of complicated wounds.

Current trends in the development of soy-based foods containing probiotics and paving the path for soy-synbiotics.

In the world of highly processed foods, special attention is drawn to the nutrient composition and safety of consumed food products. Foods fortified with probiotic bacteria confer beneficial effects on human health and are categorized as functional foods. The salubrious activities of probiotics include the synthesis of vital bioactives, prevention of inflammatory diseases, anticancerous, hypocholesterolemic, and antidiarrheal effects. Soy foods are exemplary delivery vehicles for probiotics and prebiotics and there are diverse strategies to enhance their functionality like employing mixed culture fermentation, engineering probiotics, and incorporating prebiotics in fermented soy foods. High potential is ascribed to the concurrent use of probiotics and prebiotics in one product, termed as "synbiotics," which implicates synergy, in which a prebiotic ingredient particularly favors the growth and activity of a probiotic micro-organism. The insights on emended bioactive profile, metabolic role, and potential health benefits of advanced soy-based probiotic and synbiotic hold a promise which can be profitably implemented to meet consumer needs. This article reviews the available knowledge about strategies to enhance the nutraceutical potential, mechanisms, and health-promoting effects of advanced soy-based probiotics. Traditional fermentation merged with diverse strategies to improve the efficiency and health benefits of probiotics considered vital, are also discussed.

Proposed minimal standards for description of methanogenic archaea.

Methanogenic archaea are a diverse, polyphyletic group of strictly anaerobic prokaryotes capable of producing methane as their primary metabolic product. It has been over three decades since minimal standards for their taxonomic description have been proposed. In light of advancements in technology and amendments in systematic microbiology, revision of the older criteria for taxonomic description is essential. Most of the previously recommended minimum standards regarding phenotypic characterization of pure cultures are maintained. Electron microscopy and chemotaxonomic methods like whole-cell protein and lipid analysis are desirable but not required. Because of advancements in DNA sequencing technologies, obtaining a complete or draft whole genome sequence for type strains and its deposition in a public database are now mandatory. Genomic data should be used for rigorous comparison to close relatives using overall genome related indices such as average nucleotide identity and digital DNA-DNA hybridization. Phylogenetic analysis of the 16S rRNA gene is also required and can be supplemented by phylogenies of the mcrA gene and phylogenomic analysis using multiple conserved, single-copy marker genes. Additionally, it is now established that culture purity is not essential for studying prokaryotes, and description of Candidatus methanogenic taxa using single-cell or metagenomics along with other appropriate criteria is a viable alternative. The revisions to the minimal criteria proposed here by the members of the Subcommittee on the Taxonomy of Methanogenic Archaea of the International Committee on Systematics of Prokaryotes should allow for rigorous yet practical taxonomic description of these important and diverse microbes.

Diagnosis of bacterial infection in children with relapse of nephrotic syndrome: a personalized decision-analytic nomogram and decision curve analysis.

BACKGROUND: Infections associated with nephrotic relapses (NR) are often managed according to physician preferences. A validated prediction tool will aid clinical decision-making and help in rationalizing antibiotic prescriptions. Our objective was to develop a biomarker-based prediction model and a regression nomogram for the prediction of the probability of infection in children with NR. We also aimed to perform a decision curve analysis (DCA). METHODS: This cross-sectional study included children (1-18 years) with NR. The outcome of interest was the presence of bacterial infection as diagnosed using standard clinical definitions. Total leucocyte count (TLC), absolute neutrophil count (ANC), quantitative C-reactive protein (qCRP), and procalcitonin (PCT) were the biomarker predictors. Logistic regression was used to identify the best biomarker model, followed by discrimination and calibration testing. Subsequently, a probability nomogram was constructed and DCA was done to determine the clinical utility and net benefits. RESULTS: We included 150 relapse episodes. A bacterial infection was diagnosed in 35%. Multivariate analysis showed the ANC + qCRP model to be the best predictive model. This model displayed excellent discrimination (AUC: 0.83), and calibration (optimism-adjusted intercept: 0.015, slope: 0.926). A prediction nomogram and web-application was developed. The superiority of the model was also confirmed by DCA in the probability threshold range of 15-60%. CONCLUSIONS: An ANC-based and qCRP-based internally validated nomogram can be used for the prediction of probability of infection in non-critically ill children with NR. Decision curves from this study will aid in the decision-making of empirical antibiotic therapy, incorporating threshold probabilities as a surrogate of physician preference. A higher resolution version of the Graphical abstract is available as Supplementary information.

A low-spin Fe(iii) complex with 100-ps ligand-to-metal charge transfer photoluminescence.

Transition-metal complexes are used as photosensitizers, in light-emitting diodes, for biosensing and in photocatalysis. A key feature in these applications is excitation from the ground state to a charge-transfer state; the long charge-transfer-state lifetimes typical for complexes of ruthenium and other precious metals are often essential to ensure high performance. There is much interest in replacing these scarce elements with Earth-abundant metals, with iron and copper being particularly attractive owing to their low cost and non-toxicity. But despite the exploration of innovative molecular designs, it remains a formidable scientific challenge to access Earth-abundant transition-metal complexes with long-lived charge-transfer excited states. No known iron complexes are considered photoluminescent at room temperature, and their rapid excited-state deactivation precludes their use as photosensitizers. Here we present the iron complex [Fe(btz)3]3+ (where btz is 3,3'-dimethyl-1,1'-bis(p-tolyl)-4,4'-bis(1,2,3-triazol-5-ylidene)), and show that the superior σ-donor and π-acceptor electron properties of the ligand stabilize the excited state sufficiently to realize a long charge-transfer lifetime of 100 picoseconds (ps) and room-temperature photoluminescence. This species is a low-spin Fe(iii) d5 complex, and emission occurs from a long-lived doublet ligand-to-metal charge-transfer (2LMCT) state that is rarely seen for transition-metal complexes. The absence of intersystem crossing, which often gives rise to large excited-state energy losses in transition-metal complexes, enables the observation of spin-allowed emission directly to the ground state and could be exploited as an increased driving force in photochemical reactions on surfaces. These findings suggest that appropriate design strategies can deliver new iron-based materials for use as light emitters and photosensitizers.

Microbial diversity characterizations, associated pathogenesis and antimicrobial resistance profiling of Najafgarh drain.

The Najafgarh drain plays a significant role in the pollution of the Yamuna River, accounting for 40% of the total pollution. Therefore, it is crucial to investigate and analyze the microbial diversity, metabolic functional capacity, and antibiotic resistance genes (ARGs) present in the Najafgarh drain. Additionally, studying the water quality and its relationship with the proliferation of microorganisms in the drain is of utmost importance. Results obtained confirmed the deteriorated water quality as physico-chemical parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), dissolved oxygen (DO), and total suspended solids (TSS) in the range of 125-140, 400-460, 0-0.2, 25-140.4 mg/l respectively violated the standard permissible national and global standards. In addition, the next generation sequencing (NGS) analysis confirm the presence of genus such as Thauera, Arcobacter, Pseudomonas, Geobacter, Dechloromonas, Tolumonas, Sulfurospirullum, Desulfovibrio, Aeromonas, Bacteroides, Prevotella, Cloacibacterium, Bifidobacterium, Clostridium etc. along with 864 ARGs in the wastewater obtained from the Najafgarh drain. Findings confirm that the pathogenic species reported from this dataset possess severe detrimental impact on faunal and human health. Further, Pearson's r correlation analysis indicated that environmental variables, mainly total dissolved solids (TDS) and chemical oxygen demand (COD), play a pivotal role in driving microbial community structure of this heavily polluted drain. Thus, the poor water quality, presence of a microbial nexus, pathogenic markers, and ARGs throughout this drain confirmed that it would be one potential contributor to the dissemination of disease-causing agents (pathogens) to the household and drinking water supplies in the near future.