Paroxysmal nocturnal hemoglobinuria-related thrombosis in the era of novel therapies: a 2043-patient-year analysis.

ABSTRACT: Thrombophilia is one of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anticomplement treatment has revolutionized the natural history of PNH, with control of the hemolytic process and abolition of thrombotic events (TEs). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anticoagulation depending on individual practices. Besides, a scarcity of data is present on the efficacy of direct oral anticoagulants (DOACs). Herein, we accrued a large real-world cohort of patients with PNH from 4 US centers to explore features, predictors of TE, and anticoagulation strategies. Among 267 patients followed up for a total of 2043 patient-years, 56 (21%) developed TEs. These occurred at disease onset in 43% of cases, involving more frequently the venous system, typically as Budd-Chiari syndrome. Rate of TEs was halved in patients receiving complement inhibitors (21 vs 40 TEs per 1000 patient-years in untreated cases, with a 2-year cumulative incidence of thrombosis of 3.9% vs 18.3%, respectively), and varied according to PNH granulocytes and erythrocytes clone size, type, disease activity parameters, as well as number (≥2 mutations, or less) and variant allelic frequency of PIGA mutations. Anticoagulation with warfarin (39%), DOACs (37%), and low-molecular weight heparin (16%) was administered for a median of 29 months (interquartile range [IQR], 9-61.8). No thrombotic recurrence was observed in 19 patients treated with DOACs at a median observation of 17.1 months (IQR, 8.9-45) whereas 14 cases discontinued anticoagulation without TE recurrence at a median time of 51.4 months (IQR, 29.9-86.8).

Circadian Rhythms in Cardiovascular Metabolism.

Energetic demand and nutrient supply fluctuate as a function of time-of-day, in alignment with sleep-wake and fasting-feeding cycles. These daily rhythms are mirrored by 24-hour oscillations in numerous cardiovascular functional parameters, including blood pressure, heart rate, and myocardial contractility. It is, therefore, not surprising that metabolic processes also fluctuate over the course of the day, to ensure temporal needs for ATP, building blocks, and metabolism-based signaling molecules are met. What has become increasingly clear is that in addition to classic signal-response coupling (termed reactionary mechanisms), cardiovascular-relevant cells use autonomous circadian clocks to temporally orchestrate metabolic pathways in preparation for predicted stimuli/stresses (termed anticipatory mechanisms). Here, we review current knowledge regarding circadian regulation of metabolism, how metabolic rhythms are synchronized with cardiovascular function, and whether circadian misalignment/disruption of metabolic processes contribute toward the pathogenesis of cardiovascular disease.

Expression of cell surface zinc transporter LIV1 in triple negative breast cancer is an indicator of poor prognosis and therapy failure.

Triple negative breast cancers (TNBC) are an aggressive molecular subtype of breast carcinoma (BC) identified by the lack of receptor expression for estrogen, progesterone, & human epidermal growth factor receptor-2. Lack of tangible drug targets warrants further research in TNBC. LIV1, is a zinc (Zn) transporter known to be overexpressed in few cancer types including BCs. Recently, in the United States of America, FDA approved the use of a new drug targeting LIV1, antibody drug conjugate SGN-LIV1A for treatment of TNBC patients. Though LIV1 also has a role in modulating immune cells by its differential transport of Zn, a correlation between the tumor cell expression of LIV1 and immune cell infiltrations were scantily reported. Further adequate baseline data on LIV1 expression in other populations have not been documented. Our objective was to screen a large Indian cohort of TNBC patient samples for LIV1, categorize the immune cell infiltration using CD4/CD8 expression and correlate the findings with therapy outcomes. Further, we also investigated for LIV1 expression in matched samples of primary & secondary tumors; pre & postchemotherapy in TNBC patients. Results showed an elevated expression of LIV1 in TNBC samples as compared to adjacent normal, the mean Q scores being 183.06 ± 6.39 and 120.78 ± 7.37 (p < 0.0001), respectively. Similarly, LIV1 levels were elevated in secondary tumors than primary & in patient samples postchemotherapy as compared to naïve. In the TNBC cohort, using automated method, cell morphology parameters were computed and analysis showed LIV1 levels were elevated in grade 3 TNBC samples presenting with altered cell morphology parameters namely cell size, cell perimeter, & nucleus size. Thus indicating LIV1 expressing TNBC samples portrayed an aggressive phenotype. Finally, TNBC patients with 3+ staining intensity showed poor survival (4.44 year) as compared to patients with 2+ LIV1 expression (5.47 year), emphasizing that LIV1 expression is a poor prognostic factor in TNBC. In conclusion, the study reports elevated expression of LIV1 in a large Indian TNBC cohort; high expression is a poor prognostic factor and correlated with aggressive disease and indicating the need for LIV1 targeted therapies.

Recent advancements in biomarkers, therapeutics, and associated challenges in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common type of leukemia that has a high mortality rate. The reasons for high mortality in patients with AML are therapeutic resistance, limited ability to predict duration of response, and likelihood of cancer relapse. Biomarkers, such as leukemic stem cell biomarkers, circulatory biomarkers, measurable residual disease biomarkers, and molecular biomarkers, are used for prognosis, diagnosis, and targeted killing to selectively eliminate AML cells. They also play an indispensable role in providing therapeutic resistance to patients with AML. Therefore, targeting these biomarkers will improve the outcome of AML patients. However, identifying biomarkers that can differentiate between treatment-responsive and non-responsive AML patients remains a challenge. This review discusses recent advancements in AML biomarkers, promising therapeutics, and associated challenges in the treatment of AML.

Indirect comparison of various lumen-apposing metal stents for EUS-guided biliary and gallbladder drainage: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies assessing EUS-guided biliary drainage (EUS-BD) or gallbladder drainage (EUS-GB) using lumen-apposing metal stents (LAMSs) have shown variable results based on the type of LAMS. We performed a meta-analysis of the available data. METHODS: Multiple online databases were searched for studies using LAMSs (Axios [Boston Scientific, Marlborough, Mass, USA] or Spaxus [Taewoong Medical Co, Gimpo, Korea]) for EUS-BD and EUS-GB. The outcomes of interest were technical success, clinical success, and adverse events. Pooled proportions along with 95% confidence intervals were calculated. RESULTS: A total of 18 observational studies were included: 11 for the Axios stent (433 patients; mean age, 72 years; 54% male) and 7 for the Spaxus stent (242 patients; mean age, 74 years; 50% male). The respective pooled outcomes for the Axios stent (EUS-BD and EUS-GB, respectively) were technical success, 96.2% and 96.2%; clinical success, 92.8% and 92.7%; total adverse events, 10.1% and 23.6%; and bleeding, 3.7% and 4.8%. The respective pooled outcomes for the Spaxus stent (EUS-BD and EUS-GB, respectively) were technical success, 93.8% and 95.9%; clinical success, 90.1% and 94.2%; total adverse events, 12.6% and 9.5%; and bleeding, 3.1% and 1.8%. CONCLUSIONS: Axios and Spaxus stents demonstrate similar pooled technical and clinical success rates. Adverse events occurred in 23.6% of patients (Axios stent) and 9.5% of patients (Spaxus stent) during EUS-GB.

Mechanically Flexible Self-Healing Mg(II)-Metallogel: Approach of Triggering the ROS-Induced Apoptosis in Human Breast Cancer Cells.

A self-assembly-directed thixotropic metallohydrogel (i.e., Mg-Tetrakis) of Mg(II)-metal salt and N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine (i.e., Tetrakis) was successfully achieved. The organic chemical component N,N,N',N'-tetrakis(2-hydroxy-ethyl)ethylenediamine was used as a low-molecular-weight gelator, and water was employed as the gel-forming solvent. The fabricated supramolecular metallohydrogel promisingly depicted viscoelastic and mechanoelastic behaviors, which are interpreted through various rheological parameters. The thixotropic behavior of the metallohydrogel is also well characterized through this rheological study. Field emission scanning electron microscopy microstructural analyses were performed to visualize the morphological arrangements of the metallohydrogel. The anticancer properties of the synthesized metallogels are investigated through this work. The cytotoxic potential of the metallohydrogel on the MCF-7 breast cancer cell line is critically examined. Reducing the growth of breast cancer cell line MCF-7 through the treatment of gel on the colony formation assay has been explored through the work. The antimigratory potential of the metallohydrogel on the MCF-7 cell was also scrutinized. The anticancer effect of the fabricated metallohydrogel is inspected through various assay formation strategies, like wound healing assay, tumor spheroid inhibition assay, nuclear fragmentation assay, and so on. Quantitative reactive oxygen species analysis of the cancer cells by treatment with the metallohydrogel was also conducted through this study. The mechanistic apoptosis study was executed by studying the expression of various apoptotic markers like BAX, BCL2, PUMA, and NOXA.

Genetic alteration of mRNA editing enzyme APOBEC3B in the pathogenesis of ovarian endometriosis.

RESEARCH QUESTION: What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis? DESIGN: Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models. RESULTS: Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers. CONCLUSION: The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options.

Comparative genome analysis of Pasteurella multocida strains of porcine origin.

Pasteurella multocida causes acute/chronic pasteurellosis in porcine, resulting in considerable economic losses globally. The draft genomes of two Indian strains NIVEDIPm17 (serogroup D) and NIVEDIPm36 (serogroup A) were sequenced. A total of 2182-2284 coding sequences (CDSs) were predicted along with 5-6 rRNA and 45-46 tRNA genes in the genomes. Multilocus sequence analysis and LPS genotyping showed the presence of ST50: genotype 07 and ST74: genotype 06 in NIVEDIPm17 and NIVEDIPm36, respectively. Pangenome analysis of 61 strains showed the presence of 1653 core genes, 167 soft core genes, 750 shell genes, and 1820 cloud genes. Analysis of virulence-associated genes in 61 genomes indicated the presence of nanB, exbB, exbD, ptfA, ompA, ompH, fur, plpB, fimA, sodA, sodC, tonB, and omp87 in all strains. The 61 genomes contained genes encoding tetracycline (54%), streptomycin (48%), sulphonamide (28%), tigecycline (25%), chloramphenicol (21%), amikacin (7%), cephalosporin (5%), and trimethoprim (5%) resistance. Multilocus sequence type revealed that ST50 was the most common (34%), followed by ST74 (26%), ST13 (24%), ST287 (5%), ST09 (5%), ST122 (3%), and ST07 (2%). Single-nucleotide polymorphism and core genome-based phylogenetic analysis clustered the strains into three major clusters. In conclusion, we described the various virulence factors, mobile genetic elements, and antimicrobial resistance genes in the pangenome of P. multocida of porcine origin, besides the rare presence of LPS genotype 7 in serogroup D.

Meta-Analysis of Endoscopic Full-Thickness Resection Versus Endoscopic Submucosal Dissection for Complex Colorectal Lesions.

BACKGROUND: Studies evaluating endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) for complex colorectal lesions have shown variable results. We conducted a meta-analysis of the available data. METHODS: Online databases were searched for studies comparing EFTR versus ESD for complex colorectal lesions. The outcomes of interest were resection rates, procedure time (min), and complications. Pooled odds ratios (OR) and standardized mean difference (SMD) along with 95% CI were calculated. RESULTS: A total of 4 studies with 530 patients (n=215 EFTR, n=315 ESD) were included. The mean follow-up duration was 5 months. The mean age of the patients was 68 years and 64% were men. The EFTR and ESD groups had similar rates of en bloc resection (OR: 1.73, 95% CI: 0.60-4.97, P=0.31) and R0 resection (OR: 1.52, 95% CI: 0.55-4.14, P=0.42). The EFTR group had significantly reduced procedure time (SMD -1.87, 95% CI: -3.13 to -0.61, P=0.004), total complications (OR: 0.24, 95% CI: 0.13-0.44, P<0.00001), perforation (OR: 0.12, 95% CI: 0.03-0.39, P=0.0005) and postresection electrocoagulation syndrome (OR: 0.06, 95% CI: 0.01-0.48, P=0.008). Delayed bleeding was similar in the 2 groups (OR: 0.80, 95% CI: 0.30-2.12, P=0.66). Residual/recurrent lesions were significantly higher in the EFTR group (OR: 4.67, 95% CI: 1.39-15.66, P=0.01). DISCUSSION: This meta-analysis of small studies with high heterogeneity showed that EFTR and ESD have comparable resection rates for complex colorectal lesions. EFTR is faster and has fewer complications, but it increases residual or recurrent lesions.

Comparative Vision of Nonlinear Thermo-Optical Features and Third-Order Susceptibility of Mechanically Flexible Metallosupramolecular Self-Repairing Networks with Isomeric Organic Acids.

Two self-healing-type supramolecular Ni(II)-metallogels are achieved. The choice of proper low-molecular-weight organic gelators such as trans-butenedioic acid (i.e., trans-BDA) and cis-butenedioic acid (i.e., cis-BDA) and triethylamine in N,N'-dimethylformamide solvent facilitates the metallogelation process. Through rheological investigations the mechanical robustness and viscoelastic properties of synthesized metallogels are explored. An in-depth exploration of thixotropic behavior also supports their self-healing features. Notably, distinct variations in morphologies of metallogels are also ascertained through field emission scanning electron microscopy studies. Furthermore, the existence of versatile noncovalent supramolecular interactions operating throughout the metallogel network is clearly revealed via Fourier transform infrared spectroscopy. Electrospray ionization-mass studies also explore the construction protocol of individual Ni(II)-metallogels. The Z-scan measurements with a 532 nm continuous wave laser were employed to unveil the nonlinear thermo-optical response of two synthesized self-healing metallogels, i.e., trans-BDA-TEA@Ni(II) and cis-BDA-TEA@Ni(II). Crucial parameters like the nonlinear refractive index, nonlinear absorption coefficient, thermo-optical coefficient, and third-order susceptibility of these metallogels are obtained. Metallogels show negative signs for the nonlinear refractive index and the nonlinear absorption coefficient. The real parts of the third-order susceptibility for these metallogels are much greater than the imaginary parts (i.e., χR(3) > χI(3)), making such metallogels very promising for all optical-switching applications.

Nirmatrelvir/ritonavir treatment and the risk of post-COVID condition over 180 days in Malaysia.

BACKGROUND: The effect of nirmatrelvir/ritonavir on preventing post-COVID condition (PCC) in the BA4, BA5, and XBB Omicron predominant periods is not well understood. The purpose of this study was to assess how nirmatrelvir/ritonavir treatment affected both PCC and health-related quality of life. METHODS: This retrospective cohort study enrolled 2,524 adults aged 18 years and older who were eligible for nirmatrelvir/ritonavir between July 14 to November 14, 2022. All outcomes were observed from the patient's first visit to the primary health clinic, 1 week, 1 month, 3 months, and 6 months after testing positive for COVID-19. The primary outcome was the presence of PCC. Secondary outcomes included the effects on health-related quality of life, such as walking, bathing and dressing, activities, cause adverse emotions or signs that prevent individuals from leading normal lives over a 180-day observation period. RESULTS: There were no significant differences observed between the nirmatrelvir/ritonavir and those not administered (control group) in terms of PCC symptoms at 3 months (OR 0.71 95% CI 0.31, 1.64) and 6 months (OR 1.30 95% CI 0.76, 2.21). At 3 months, the use of nirmatrelvir/ritonavir was associated with a 26% reduction in symptoms causing negative emotions (OR 0.74 95% CI 0.60, 0.92) and an increased likelihood of symptoms limiting walking (OR 1.58 95% CI 1.10, 2.27). However, there were no significant differences between the nirmatrelvir/ritonavir and the control group in terms of the impact of PCC on health-related quality of life at 6 months. CONCLUSIONS: Our study indicates that the administration of nirmatrelvir/ritonavir does not significantly reduce PCC after 3 months and 6 months in a population with high vaccination coverage.

Synthesis of Carbon Dots from Peltophorum Pterocarpum Flowers for Selective Fluorescence Detection of Carbendazim.

In this study, carbon dots (CDs) were synthesized from Peltophorum pterocarpum flowers as the precursor material using the hydrothermal method. The fluorescence emission spectra of the resulting Peltophorum pterocarpum CDs (PP-CDs) exhibited excitation-independent behavior, showing the fluorescence emission peak at 410 nm when excited at 330 nm. This method is simple, rapid and well consistent with the green chemistry and sustainable analytical method development. The as-synthesized PP-CDs acted as a promising fluorescent probe for detecting carbendazim (CBZ) via aggregation-induced emission mechanism, showing a linear response to CBZ concentrations ranging from 1 to 30 µM, with a detection limit of 5.41 nM. This method was successfully applied to quantify CBZ in food samples, achieving excellent recoveries of 99% with a relative standard deviation (RSD) of less than 2%.

Green Emissive Molybdenum Nanoclusters for Selective and Sensitive Detection of Hydroxyl Radical in Water Samples.

In this work, Cassia tora (C. tora) have been used as a template to synthesize green fluorescent C. tora molybdenum nanoclusters (C. tora-MoNCs) through a green chemistry approach. These C. tora-MoNCs showed a quantum yield (QY) of 7.72% and exhibited a significant emission peak at 498 nm when excited at 380 nm. The as-prepared C. tora-MoNCs had an average size of 3.48 ± 0.80 nm and showed different surface functionality. The as-synthesized C. tora-MoNCs were successfully identified the hydroxyl radical (•OH) via a fluorescence quenching mechanism. Also, fluorescence lifetime and Stern-Volmer proved that after the addition of •OH radicals it was quenched the fluorescence intensity via a static quenching mechanism. The limit of detection is 9.13 nM, and this approach was successfully utilized for sensing •OH radicals in water samples with a good recovery rate.

Green Synthetic Approach for the Preparation of Blue Emitting Gold Nanoclusters: A Simple Analytical Method for Detection of Hexaconazole Fungicide.

Blue emissive Argyreia nervosa-capped gold nanoclusters (A. nervosa-AuNCs) were synthesized via a simple environment-friendly method. The developed probe exhibits rapid response towards the target analyte (hexaconazole fungicide). Several characterizations, including FT-IR, UV-visible, fluorescence, HR-TEM, XPS, and fluorescence lifetime, were studied to confirm the formation of A. nervosa-AuNCs. The A. nervosa-AuNCs displayed emission and excitation peaks at 470 and 390 nm, respectively. Furthermore, the quantum yield (QY) of A. nervosa-AuNCs was 21.25%. The as-synthesized A. nervosa-AuNCs showed a good linear response with hexaconazole in the concentration range of 0.025-180 µM, with a detection limit (LOD) of 21.94 nM, indicating A. nervosa-AuNCs could be used as a sensitive and selective probe for detecting hexaconazole through a fluorescence "turn-off" mechanism. The A. nervosa-AuNCs were successfully used to detect hexaconazole in real samples. Moreover, A. nervosa-AuNCs were used as a bio-imaging probe for visualization of Saccharomyces cerevisiae cells.

A short RP tachycardia in congenitally corrected transposition. What is the mechanism?

A 51-year-old female with congenitally corrected transposition of great arteries (CCTGA), situs solitus, dextrocardia, atrial septal defect and persistent left superior vena cava underwent electrophysiology study for recurrent palpitations with documented narrow complex, short RP tachycardia. With a catheter in the region of the anterior mitral annulus, a His signal was recorded and HV interval was 35 msec. Tachycardia was induced with a ventricular extrastimulus. During the tachycardia there was 1:1 ventriculo-atrial conduction and central atrial activation with a VA interval of 20 msec. The recorded His signal could be seen after the QRS. What is the mechanism of the tachycardia?

Renal resistive index by point of care ultrasound to predict sepsis associated acute kidney injury in critically ill children.

BACKGROUND: Sepsis associated acute kidney injury (AKI) is linked with adverse outcomes in the PICU. Doppler-based renal resistive index (RRI) has shown promising results in adults for prediction of AKI. We aimed to explore the performance of RRI in children with sepsis. METHODS: This prospective observational study (March - November 2022) included children aged 1-12 years with sepsis admitted to the PICU. RRI and urine neutrophil gelatinase associated lipocalin (NGAL) were measured within 12 h of admission. Children were followed up for 3 days. AKI (new and persistent) was defined as any child with KDIGO stage 2 or 3 AKI on day 3. RESULTS: We enrolled 90 children but included 79 in final analysis. Two thirds (n = 53, 67%) had septic shock. Median (IQR) age was 6.2 years (4.1-9.2). RRI decreased with increasing age. Twenty-six (33%) children had AKI on day 3. Mean (SD) RRI was higher in the AKI group [0.72 (0.08) vs. 0.65 (0.07), p < 0.001].The area under ROC curve for RRI to detect AKI among the 1-4 year old group was 0.75 (95% CI:0.51, 0.98; p = 0.05) and among the 5-12 year old group was 0.76 (0.62, 0.89; p = 0.001). An RRI 0.71 predicted AKI with 100% sensitivity and 46.2% specificity among the 1-4-year-old group and RRI 0.69 predicted it with 70% sensitivity and 77.5% specificity in the 5-12-year-old group. RRI and eGFR at admission were independent predictors of AKI on multivariable analysis. Urine NGAL 94.8 ng/ml predicted AKI with 76.9% sensitivity and 77.4% specificity and AUROC was 0.74 (0.62, 0.86) among the 1-12-year-old group. CONCLUSIONS: RRI values varied with age. RRI showed good diagnostic accuracy to detect new/persistent AKI on day 3 in children with sepsis; however, it was less precise as an independent predictor.

Sustainable pathways for solar desalination using nanofluids: A critical review.

Water is a fundamental requirement for the survival of human beings. Although water is abundantly available across the globe, access to freshwater still remains a major concern. Most of the water available is saline or brackish, which is not fit for human consumption. Desalination is the optimum solution for production of potable water from saline water. A major shortcoming of conventional desalination technologies is their dependence on fossil fuel that results in environmental degradation, global warming, etc. Therefore, sustainable desalination technology has evolved as a need of hour. Among all renewable energy resources, solar energy is abundantly available and can be potentially harvested. Therefore, solar energy can be used to drive sustainable desalination technologies. A solar still converts saline water into freshwater in a single step using solar energy. But the major drawbacks of solar still are relatively lower efficiency and lower yield. Nanofluids are widely used to overcome these limitations due to their extraordinary and unique properties. This paper critically reviews the recent research performed on the application of nanofluids in solar desalination systems. Methods of nanofluid preparation, their types and properties are also discussed in detail. Application of nanofluids in solar desalination systems is discussed with special attention on performance enhancement of solar stills. Combinations of nanofluids with various other performance enhancement techniques are also considered. The effectiveness of nanofluids in solar stills is found to be dependent majorly on the nature and concentration of the nanofluid used.

Analysing the performance of the NARX model for forecasting the water level in the Chikugo River estuary, Japan.

Estuaries are dynamic environments which are driven by various natural processes like river discharge, tides, waves, influx of saline water and sediments, etc. These ecosystems are the most sensitive to sea level rise and fluctuations in river discharge associated with climate change. A direct response of sea level rise and river discharge can be observed in the water level of estuaries. However, existing models have not considered these parameters for forecasting water level. This paper focuses on developing a water level forecast model for the Chikugo River estuary in Japan using Nonlinear Autoregressive with Exogenous inputs (NARX Model). NARX neural network was used to do the one-step-ahead prediction of water level considering the various parameters that can very well be influenced by climate change: previous water level, river discharge, and salinity. Accordingly, three models were developed: (i) Model I considering previous water level; (ii) Model II additionally considering river discharge; and (iii) Model III additionally considering salinity. All the models showed appreciable performance in forecasting the water level. Model III had the best correlation with the water level with a cross-correlation value of 0.6030, while the river discharge had only a cross-correlation of 0.1113 indicating that the Chikugo River estuary is tide-dominated. The model was trained using different combinations of available data - previous water level, river discharge, and salinity. Cross-correlation results showed a better correlation between water level and salinity than various other combinations trained. Therefore, tidal intrusion influences the water level in the estuary, thereby depicting that sea level rise can affect the water level, and its influence can be well predicted by the developed model. The water level significantly affects the flora and fauna and the predictability of future estuarine floods can help in taking necessary mitigation strategies.

Severe Pneumonia in PICU Admissions: The Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) Observational Cohort Study, 2020-2022.

OBJECTIVES: Mortality from pneumonia is three times higher in Asia compared with industrialized countries. We aimed to determine the epidemiology, microbiology, and outcome of severe pneumonia in PICUs across the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN). DESIGN: Prospective multicenter observational study from June 2020 to September 2022. SETTING: Fifteen PICUs in PACCMAN. PATIENTS: All children younger than 18 years old diagnosed with pneumonia and admitted to the PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical, microbiologic, and outcome data were recorded. The primary outcome was PICU mortality. Univariate and multivariable logistic regression was performed to investigate associations between PICU mortality and explanatory risk factors on presentation to the PICU. Among patients screened, 846 of 11,778 PICU patients (7.2%) with a median age of 1.2 years (interquartile range, 0.4-3.7 yr) had pneumonia. Respiratory syncytial virus was detected in 111 of 846 cases (13.1%). The most common bacteria were Staphylococcus species (71/846 [8.4%]) followed by Pseudomonas species (60/846 [7.1%]). Second-generation cephalosporins (322/846 [38.1%]) were the most common broad-spectrum antibiotics prescribed, followed by carbapenems (174/846 [20.6%]). Invasive mechanical ventilation and noninvasive respiratory support was provided in 438 of 846 (51.8%) and 500 of 846 (59.1%) patients, respectively. PICU mortality was 65 of 846 (7.7%). In the multivariable logistic regression model, age (adjusted odds ratio [aOR], 1.08; 95% CI, 1.00-1.16), Pediatric Index of Mortality 3 score (aOR, 1.03; 95% CI, 1.02-1.05), and drowsiness (aOR, 2.73; 95% CI, 1.24-6.00) were associated with greater odds of mortality. CONCLUSIONS: In the PACCMAN contributing PICUs, pneumonia is a frequent cause for admission (7%) and is associated with a greater odds of mortality.

Developing a roadmap to reach and sustain 90% full immunization coverage through a cross-sectoral system strengthening strategy in Bihar, India.

INTRODUCTION: Reducing childhood mortality by curtailing the incidence of vaccine preventable diseases is contingent upon a robust and high-performing routine immunization system. According to the available data, the full immunization coverage (FIC) in the state of Bihar (India) has reached ~ 71%. While the government aspires to reach 90% FIC, a systematic evidence-based investigation of the reasons behind underimmunization as well as the identification of drivers and enablers to reach and sustain 90% FIC is critical. This study aimed to review the factors leading to underimmunized children in the state of Bihar and develop a forward-looking roadmap to reach and sustain 90% FIC by adopting a system strengthening approach. METHOD: We conducted a desk review, followed by extensive stakeholder interviews and field visits to document and analyze the data and evidence relevant to routine immunization system performance in the state of Bihar. The stakeholders included the State Immunization Officer, District Immunization Officers, Block-level health officials, representatives from development agencies, healthcare workers, and caregivers. A total of eighty-six structured interviews were conducted, which included qualitative and quantitative parameters. RESULT: While positive results were observed from the assessment of Bihar's immunization system, the implementation of targeted strategies for supply, service delivery and demand can provide a means to achieve FIC of 90%. The roadmap developed by the Government of Bihar enlists 40 + interventions across key thematic areas and has been prioritized over a 5-year time horizon as short, medium, and long-term milestones to achieve 90% FIC. These interventions include strengthening the data availability and quality, improving the governance and review mechanism, augmenting the capacity of health workers involve with immunization programme, and initiatives to increase demand for immunization services. CONCLUSION: The Bihar's Immunization Roadmap development project work follows a methodical approach to assess and identify intervention to improve immunization coverage and can provide information and reference to other states and countries that are aiming to formulate similar action plans.