Enhancing efficacy of the MEK inhibitor trametinib with paclitaxel in KRAS -mutated colorectal cancer.

Background: KRAS is frequently mutated in the tumors of patients with metastatic colorectal cancer (mCRC) and thus represents a valid target for therapy. However, the strategies of targeting KRAS directly and targeting the downstream effector mitogen-activated protein kinase kinase (MEK) via monotherapies have shown limited efficacy. Thus, there is a strong need for novel, effective combination therapies to improve MEK-inhibitor efficacy in patients with KRAS -mutated mCRC. Objective: Our objective was to identify novel drug combinations that enhance MEK-inhibitor efficacy in patients with KRAS -mutated mCRC. Design: In this study, we performed unbiased high-throughput screening (HTS) to identify drugs that enhance the efficacy of MEK inhibitors in vitro , and we validated the efficacy of the drugs in vivo . Methods: HTS was performed using 3-dimensional CRC spheroids. Trametinib, the anchor drug, was probed with 2 clinically ready libraries of 252 drugs to identify effective drug combinations. The effects of the drug combinations on CRC cell proliferation and apoptosis were further validated using cell growth assays, flow cytometry, and biochemical assays. Proteomic and immunostaining studies were performed to determine the effects of the drugs on molecular signaling and cell division. The effects of the drug combinations were examined in vivo using CRC patient-derived xenografts. Results: HTS identified paclitaxel as being synergistic with trametinib. In vitro validation showed that, compared with monotherapies, this drug combination demonstrated strong inhibition of cell growth, reduced colony formation, and enhanced apoptosis in multiple KRAS -mutated CRC cell lines. Mechanistically, combining trametinib with paclitaxel led to alterations in signaling mediators that block cell cycle progression and increases in microtubule stability that resulted in significantly higher defects in the mitosis. Finally, the combination of trametinib with paclitaxel exhibited significant inhibition of tumor growth in several KRAS -mutant patient-derived xenograft mouse models. Conclusion: Our data provide evidence supporting clinical trials of trametinib with paclitaxel as a novel therapeutic option for patients with KRAS -mutated, metastatic CRC.

Demand-driven capacity building for public health nutrition research in Lao PDR.

In Laos, rates of undernutrition, especially among children under 5 years of age, remain high. In response, a large multidisciplinary team embarked on a multi-year project in Laos beginning in 2019 with the purpose of institutional strengthening around public health nutrition research. This paper summarizes the Applied Nutrition Research Capacity Building project's activities, immediate project results, and prospects for sustaining impacts into the future. Eight primary activities were undertaken, including back-office strengthening, mentored research, and curriculum review and development. Requested training and skill development in areas related to public health nutrition, anthropometry, and research methods reached more than 1000 professionals. The first edition of a Lao-English Nutrition Glossary was produced, as was the country's first National Nutrition Research Agenda, a document which sets locally-identified priorities for future research. Project success was achieved by focusing on the priorities of project partners and the Lao government, as articulated in the Lao National Nutrition Strategy and Action Plan. Project design elements that could guide similar efforts undertaken elsewhere include multi-year engagement, an emphasis on sustained peer mentorship, and the use of an extended period of pre-planning in collaboration with project stakeholders prior to the start of activities.

Study of Urinary Electrolytes and Fractional Excretion of Uric Acid in Evaluating Hyponatremia.

INTRODUCTION: Serum sodium levels <135 mmol/L are known as hyponatremia. The syndrome of inappropriate antidiuresis (SIAD), which is described by a drop in the effective arterial blood volume (EABV), is the most common cause of hyponatremia. This study was carried out to categorize hyponatremia based on volume status and on parameters like fractional excretion of uric acid (FE-UA), fractional excretion of sodium (FE-Na), urine uric acid (U-UA), and serum uric acid (SR-UA) values. MATERIALS AND METHODS: Sixty-one patients admitted to the Department of Medicine at Rajendra Institute of Medical Sciences (RIMS), Ranchi, with hyponatremia were included in the study by applying random sampling. Routine urine and blood samples were collected for biochemical tests. Institutional ethical clearance was obtained for this study. Data were analyzed using Statistical Package for the Social Sciences (SPSS) (version 21). Frequency, central tendency, receiver operating characteristic (ROC), and nonparametric Mann-Whitney U test analysis tools were utilized for analysis. RESULTS: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) was found in nearly 50.82% of hyponatremic patients. Approximately, 70% of non-SIADH patients were hypovolemic. When compared to the non-SIADH group, patients in the SIADH group had significantly higher systolic blood pressure (SBP) and diastolic blood pressure (DBP), lower pulse rates, and lower urine creatinine levels and urine creatinine to serum creatinine ratio. The non-SIADH group had significantly higher SR-UA levels (p < 0.0001), but the SIADH group had significantly higher U-UA levels and significantly lower SR-UA levels. Among the studied parameters, FE-UA was the most accurate in diagnosing SIADH. FE-UA (>12%) is a better diagnostic marker for distinguishing SIADH patients from non-SIADH patients. CONCLUSION: FE-uric acid was found to be the most superior in diagnosing SIADH, followed by FE-Na.

BATF is a major driver of NK cell epigenetic reprogramming and dysfunction in AML.

Myelodysplastic syndrome and acute myeloid leukemia (AML) belong to a continuous disease spectrum of myeloid malignancies with poor prognosis in the relapsed/refractory setting necessitating novel therapies. Natural killer (NK) cells from patients with myeloid malignancies display global dysfunction with impaired killing capacity, altered metabolism, and an exhausted phenotype at the single-cell transcriptomic and proteomic levels. In this study, we identified that this dysfunction was mediated through a cross-talk between NK cells and myeloid blasts necessitating cell-cell contact. NK cell dysfunction could be prevented by targeting the αvß-integrin/TGF-ß/SMAD pathway but, once established, was persistent because of profound epigenetic reprogramming. We identified BATF as a core transcription factor and the main mediator of this NK cell dysfunction in AML. Mechanistically, we found that BATF was directly regulated and induced by SMAD2/3 and, in turn, bound to key genes related to NK cell exhaustion, such as HAVCR2, LAG3, TIGIT, and CTLA4. BATF deletion enhanced NK cell function against AML in vitro and in vivo. Collectively, our findings reveal a previously unidentified mechanism of NK immune evasion in AML manifested by epigenetic rewiring and inactivation of NK cells by myeloid blasts. This work highlights the importance of using healthy allogeneic NK cells as an adoptive cell therapy to treat patients with myeloid malignancies combined with strategies aimed at preventing the dysfunction by targeting the TGF-ß pathway or BATF.

A parameter free relative density based biclustering method for identifying non-linear feature relations.

The existing biclustering algorithms often depend on assumptions like monotonicity or linearity of feature relations for finding biclusters. Though a few algorithms overcome this problem using density-based methods, they tend to miss out many biclusters because they use global criteria for identifying dense regions. The proposed method, PF-RelDenBi, uses local variations in marginal and joint densities for each pair of features to find the subset of observations, forming the basis of the relation between them. It then finds the set of features connected by a common set of observations using a non-linear feature relation index, resulting in a bicluster. This approach allows us to find biclusters based on feature relations, even if the relations are non-linear or non-monotonous. Additionally, the proposed method does not require the user to provide any parameters, allowing its application to datasets from different domains. To study the behaviour of PF-RelDenBi on datasets with different properties, experiments were carried out on sixteen simulated datasets and the performance has been compared with eleven state-of-the-art algorithms. The proposed method is seen to produce better results for most of the simulated datasets. Experiments were conducted with five benchmark datasets and biclusters were detected using PF-RelDenBi. For the first two datasets, the detected biclusters were used to generate additional features that improved classification performance. For the other three datasets, the performance of PF-RelDenBi was compared with the eleven state-of-the-art methods in terms of accuracy, NMI and ARI. The proposed method is seen to detect biclusters with greater accuracy. The proposed technique has also been applied to the COVID-19 dataset to identify some demographic features that are likely to affect the spread of COVID-19.

Hydro-chemical characterization and irrigation suitability assessment of a tropical decaying river in India.

Water pollution is a major concern for a decaying river. Polluted water reduces ecosystem services and human use of rivers. Therefore, the present study aims to assess the irrigation suitability of the Jalangi River water. A total of 34 pre-selected water samples were gathered from the source to the sink of the Jalangi River with an interval of 10 km and one secondary station's data from February 2012 to January 2022 were used for this purpose. The Piper diagram exhibits that the Jalangi River water is Na+-HCO3- types, and the alkaline earth (Ca2+ + Mg2+) outperforms alkalises (Na+ + K+) and weak acids (HCO3- + CO32-) outperform strong acids (Cl- + SO42-). SAR values ranging from 0.35 to 0.64 show that water is suitable for irrigation and poses no sodicity risks. The %Na results show that 91.18% of water samples are good and acceptable for irrigation. RSC levels indicate a significant alkalinity hazard, with 94.12% of samples considered inappropriate for irrigation. PI findings show that 91.18% of water samples are suitable for irrigation. Apart from the spatial water samples, seasonal water samples exhibit a wide variations as per the nature of irrigation hazards. Gibbs plot demonstrates that the weathering of rocks determined the hydro-chemical evolution of Jalangi River water. This study identifies very little evaporation dominance for pre- and post-monsoon water. The analysis of variance (ANOVA) test illustrates that there are no spatial variations in water quality while seasonal variations are widely noted (p < 0.05). The results also revealed that river water for irrigation during monsoon is suitable compared to the pre-monsoon season. Anthropogenic interventions including riverbed agriculture, and the discharge of untreated sewage from urban areas are playing a crucial role in deteriorating the water quality of the river, which needs substantial attention from the various stakeholders in a participatory, and sustainable manner.

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion.

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.

Quantitative assessment of machine learning reliability and resilience.

Advances in machine learning (ML) have led to applications in safety-critical domains, including security, defense, and healthcare. These ML models are confronted with dynamically changing and actively hostile conditions characteristic of real-world applications, requiring systems incorporating ML to be reliable and resilient. Many studies propose techniques to improve the robustness of ML algorithms. However, fewer consider quantitative techniques to assess changes in the reliability and resilience of these systems over time. To address this gap, this study demonstrates how to collect relevant data during the training and testing of ML suitable for the application of software reliability, with and without covariates, and resilience models and the subsequent interpretation of these analyses. The proposed approach promotes quantitative risk assessment of ML technologies, providing the ability to track and predict degradation and improvement in the ML model performance and assisting ML and system engineers with an objective approach to compare the relative effectiveness of alternative training and testing methods. The approach is illustrated in the context of an image recognition model, which is subjected to two generative adversarial attacks and then iteratively retrained to improve the system's performance. Our results indicate that software reliability models incorporating covariates characterized the misclassification discovery process more accurately than models without covariates. Moreover, the resilience model based on multiple linear regression incorporating interactions between covariates tracks and predicts degradation and recovery of performance best. Thus, software reliability and resilience models offer rigorous quantitative assurance methods for ML-enabled systems and processes.

Effect of channel morphological changes on wetland transformation.

Keeping aside the traditional approaches to investigating floodplain wetland transformation, the current study investigated various aspects of it through changes in river channel morphology and drainage pattern. The study analyzed wetland transformation using satellite image-based machine learning and intensive fieldwork. Ordinary Least Square (OLS) regression was applied to identify dominant influencing factors among 24 contributing factors under six clusters to eight dependent phenomena of transformation. The result showed that 57 % of wetland area lost since 1991, and existing wetland has also experiencing hydrological scarcity. From 1991 to 2021, the area under low water depth (<1 m.) inflated from 18.55 % to 50.54 %, the hydro-period narrowed down, and the appearance of water become inconsistent. The OLS result showed that changes in channel morphology (bottle neck channel, embankment-driven carrying capacity enhancement, etc.), interruptions in river and wetland connecting channels (source closure, breaching the continuity, conversion in to agricultural land, etc.), and changes in flood ambience (regulated by dam construction, erection of embankments, etc.) majorly contributed to wetland transformation. Very high explainability was found in the cases of rate of wetland loss, decreasing water depth under greater depth, narrowing hydro-period (R2 > 0.9). The findings of this work would be a good policy document for floodplain wetland management.

How hydrological components of urban blue space influence the thermal milieu?

Present study examines the possible improvement of thermal discomfort mitigation. Unlike prior researches, which focused primarily on cooling effects of urban blue space, this study, instead of physical presence of blue space considers its hydrological components. The aim of the study is to better understand the role hydrological components like water consistency depth etc. In temperature regulation. The work uses field surveys and modeling to demonstrate how these hydrological factors influence the cooling effect of blue space, providing insights on urban thermal management. To fulfill the purpose, spatial association of hydrological components blue space with its thermal environment and cooling effects was assessed. The control of hydrological components on the surrounding air temperature was examined by conducting case studies. RESULTS: reveals greater hydro-duration, deeper water, and higher Water Presence Frequency (WPF) produce greater cooling effects. The study demonstrates a favorable correlation between hydrological richness and temperature reduction. The study also analyzes how land use and wetland size affect temperature, emphasizing the significance of hydrological conservation and restoration for successful temperature mitigation. Due to their hydrology, larger wetlands are able to moderate temperature to some extent, whereas smaller, fragmented wetlands being hydrologically poor are not so influential in this regard. With these results, the present study reaches beyond to the general understanding regarding the cooling effects of the urban blue spaces. While the previous studies primarily focused on estimating the cooling effect of urban blue space, the current one shows its synchronization with the hydrological characteristics. Novelty also entrusts here, through the modeling and field survey current study demonstrates deeper and consistent water coverage in the urban blue space for maximum period of a year pronounces the cooling effect. In addition, in this cooling effect, the role of land use which is a strong determinant of many aspects of the urban environment is also highlighted. Since all these findings define specific hydrological feature, the study has several practical implications. Mare restoration of urban blue space is not enough to mitigate the thermal discomfort. In order to optimize the cooling effect, the conservation of the hydrological richness is essential. The hydrological richness of the smaller wetlands and the edge of the larger wetlands is to be improved. The connection of these wetlands with the adjacent mighty may strengthen the hydrology. The vegetation was found to promote the cooling effect whereas shorter building helped in spreading the cooling effect. Such finding drives to incorporate the blue space with the green infrastructure along with restricting the building height atleast at the edge of the blue space.

Contribution of Food from Market Purchases and Home Production to Child Nutrient Intake: Evidence from the EFFECTS Study Baseline Data.

BACKGROUND: Child undernutrition is prevalent in Tanzania, and households rely primarily on local markets and home production as food sources. However, little is known about the contribution of food market purchases to nutrient intakes among children consuming complementary foods. OBJECTIVES: To quantify the relationships between diversity of foods purchased and produced by households and adequate child nutrient intake in Mara, Tanzania. METHODS: Cross-sectional baseline dietary and household food source data from the Engaging Fathers for Effective Child Nutrition and Development in Tanzania study were collected from mothers of 586 children aged 9-23 mo clustered in 80 villages in Mara, Tanzania. We conducted mixed effects linear regressions to quantify the association between the diversity of foods consumed at home, from market purchases and home production, and nutrient intake adequacy (based on 24-h food recalls). RESULTS: Children had inadequate diets, with fewer than half of children consuming adequate amounts of vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B9 (folate), calcium, iron, and zinc. Breastfeeding was associated with higher overall mean adequacy (b = 0.15-0.19 across models, P < 0.001). Diversity of foods purchased was positively associated with the intake of vitamin B12 and calcium (both P < 0.001); this effect was attenuated among breastfed children. Among nonbreastfed children, production diversity was positively associated with vitamin A intake (b=0.04; P < .05) but not with intake of other nutrients. CONCLUSIONS: Both household food purchase and food production diversities were positively associated with children's nutrient intake in rural Mara, Tanzania. Nutrition programming should consider the role of food markets in addition to home food production to improve child diets. This trial was registered at clinicaltrials.gov as NCT03759821, https://clinicaltrials.gov/study/NCT03759821.

Impact of sunitinib resistance on clear cell renal cell carcinoma therapeutic sensitivity in vitro.

Sunitinib resistance creates a major clinical challenge for the treatment of advanced clear cell renal cell carcinoma (ccRCC) and functional and metabolic changes linked to sunitinib resistance are not fully understood. We sought to characterize the molecular and metabolic changes induced by the development of sunitinib resistance in ccRCC by developing and characterizing two human ccRCC cell lines resistant to sunitinib. Consistent with the literature, sunitinib-resistant ccRCC cell lines presented an aberrant overexpression of Axl and PD-L1, as well as a metabolic rewiring characterized by enhanced OXPHOS and glutamine metabolism. Therapeutic challenges of sunitinib-resistant ccRCC cell lines in vitro using small molecule inhibitors targeting Axl, AMPK and p38, as well as using PD-L1 blocking therapeutic antibodies, showed limited CTL-mediated cytotoxicity in a co-culture model. However, the AMPK activator metformin appears to sensitize the effect of PD-L1 blocking therapeutic antibodies and to enhance CTLs' cytotoxic effects on ccRCC cells. These effects were not broadly observed with the Axl and the p38 inhibitors. Taken together, these data suggest that targeting certain pathways aberrantly activated by sunitinib resistance such as the AMPK/PDL1 axis might sensitize ccRCC to immunotherapies as a second-line therapeutic approach.

Anthropogenic impacts on urban blue space and its reciprocal effect on human and socio-ecological health.

Quantifying anthropogenic impacts on blue space (BS) and its effect on human and socio-ecological health was least explored. The present study aimed to do this in reference to the urban BS transformation scenario of Eastern India. To measure BS transformation, Landsat image-based water indices were run from 1990 to 2021. Anthropogenic impact score (AIS) and 7 components scores of 78 selected BS on 70 parameters related data driven from the field. Total 345 respondents were taken for human and socio-ecological health assessment. For this, depression (DEP), anxiety (ANX), stress (STR), physical activities (PA), social capital (SC), therapeutic landscape (TL) and environment building (EB) parameters were taken. The result exhibited that BS was reduced. About 50% of urban core BS was reported highly impacted. Human and socio-ecological health was identified as good in proximity to BS, but it was observed better in the cases of larger peripheral BS. AIS on BS was found to be positively associated with mental health (0.47-0.63) and negatively associated with PA, SC, TL and EB (-0.50 to -0.90). Standard residual in ordinary least square was reported low (-1.5 to 1.5) in 95% BS. Therefore, BS health restoration and management is crucial for sustaining the living environment.

ComplexEye: a multi-lens array microscope for high-throughput embedded immune cell migration analysis.

Autonomous migration is essential for the function of immune cells such as neutrophils and plays an important role in numerous diseases. The ability to routinely measure or target it would offer a wealth of clinical applications. Video microscopy of live cells is ideal for migration analysis, but cannot be performed at sufficiently high-throughput (HT). Here we introduce ComplexEye, an array microscope with 16 independent aberration-corrected glass lenses spaced at the pitch of a 96-well plate to produce high-resolution movies of migrating cells. With the system, we enable HT migration analysis of immune cells in 96- and 384-well plates with very energy-efficient performance. We demonstrate that the system can measure multiple clinical samples simultaneously. Furthermore, we screen 1000 compounds and identify 17 modifiers of migration in human neutrophils in just 4 days, a task that requires 60-times longer with a conventional video microscope. ComplexEye thus opens the field of phenotypic HT migration screens and enables routine migration analysis for the clinical setting.

Integrated Meta-Omics Analysis Unveils the Pathways Modulating Tumorigenesis and Proliferation in High-Grade Meningioma.

Meningioma, a primary brain tumor, is commonly encountered and accounts for 39% of overall CNS tumors. Despite significant progress in clinical research, conventional surgical and clinical interventions remain the primary treatment options for meningioma. Several proteomics and transcriptomics studies have identified potential markers and altered biological pathways; however, comprehensive exploration and data integration can help to achieve an in-depth understanding of the altered pathobiology. This study applied integrated meta-analysis strategies to proteomic and transcriptomic datasets comprising 48 tissue samples, identifying around 1832 common genes/proteins to explore the underlying mechanism in high-grade meningioma tumorigenesis. The in silico pathway analysis indicated the roles of extracellular matrix organization (EMO) and integrin binding cascades in regulating the apoptosis, angiogenesis, and proliferation responsible for the pathobiology. Subsequently, the expression of pathway components was validated in an independent cohort of 32 fresh frozen tissue samples using multiple reaction monitoring (MRM), confirming their expression in high-grade meningioma. Furthermore, proteome-level changes in EMO and integrin cell surface interactions were investigated in a high-grade meningioma (IOMM-Lee) cell line by inhibiting integrin-linked kinase (ILK). Inhibition of ILK by administrating Cpd22 demonstrated an anti-proliferative effect, inducing apoptosis and downregulating proteins associated with proliferation and metastasis, which provides mechanistic insight into the disease pathophysiology.

Vincristine Enhances the Efficacy of MEK Inhibitors in Preclinical Models of KRAS-mutant Colorectal Cancer.

Mutations in KRAS are found in more than 50% of tumors from patients with metastatic colorectal cancer (mCRC). However, direct targeting of most KRAS mutations is difficult; even the recently developed KRASG12C inhibitors failed to show significant benefit in patients with mCRC. Single agents targeting mitogen-activated protein kinase kinase (MEK), a downstream mediator of RAS, have also been ineffective in colorectal cancer. To identify drugs that can enhance the efficacy of MEK inhibitors, we performed unbiased high-throughput screening using colorectal cancer spheroids. We used trametinib as the anchor drug and examined combinations of trametinib with the NCI-approved Oncology Library version 5. The initial screen, and following focused validation screens, identified vincristine as being strongly synergistic with trametinib. In vitro, the combination strongly inhibited cell growth, reduced clonogenic survival, and enhanced apoptosis compared with monotherapies in multiple KRAS-mutant colorectal cancer cell lines. Furthermore, this combination significantly inhibited tumor growth, reduced cell proliferation, and increased apoptosis in multiple KRAS-mutant patient-derived xenograft mouse models. In vivo studies using drug doses that reflect clinically achievable doses demonstrated that the combination was well tolerated by mice. We further determined that the mechanism underlying the synergistic effect of the combination was due to enhanced intracellular accumulation of vincristine associated with MEK inhibition. The combination also significantly decreased p-mTOR levels in vitro, indicating that it inhibits both RAS-RAF-MEK and PI3K-AKT-mTOR survival pathways. Our data thus provide strong evidence that the combination of trametinib and vincristine represents a novel therapeutic option to be studied in clinical trials for patients with KRAS-mutant mCRC. SIGNIFICANCE: Our unbiased preclinical studies have identified vincristine as an effective combination partner for the MEK inhibitor trametinib and provide a novel therapeutic option to be studied in patients with KRAS-mutant colorectal cancer.

Factors influencing and changes in childhood vaccination coverage over time in Bangladesh: a multilevel mixed-effects analysis.

INTRODUCTION: This study aimed to investigate the associated factors and changes in childhood vaccination coverage over time in Bangladesh. METHODS: Bangladesh's Demographic and Health Surveys from 2011, 2014, and 2017-18 provided data for this study on vaccination coverage among children aged 12 to 35 months. For three survey periods, multilevel binary logistic regression models were employed. RESULTS: The overall prevalence (weighted) of full vaccination among children aged 12-35 months were 86.17% in 2011, 85.13% in 2014, and 89.23% in 2017-18. Children from families with high wealth index, mothers with higher education, and over the age of 24 and who sought at least four ANC visits, as well as children from urban areas were more likely to receive full vaccination. Rangpur division had the highest change rate of vaccination coverage from 2011 to 2014 (2.26%), whereas Sylhet division had the highest change rate from 2014 to 2017-18 (34.34%). CONCLUSION: To improve immunization coverage for Bangladeshi children, policymakers must integrate vaccine programs, paying special attention to mothers without at least a high school education and families with low wealth index. Increased antenatal care visits may also aid in increasing the immunization coverage of their children.

Protocol to Assess the Biological Activity of Insulin Glargine, Insulin Lispro, and Insulin Aspart In Vitro.

Insulin is a hormone produced by ß-cells of the pancreas and controls the amount of sugar in the blood. Since its discovery over 100 years ago, insulin has been used as a life-saving treatment for people with diabetes. Historically, the biological activity or bioidentity of insulin products has been assessed using an in vivo model. However, reduction in animal experiments is a goal for many worldwide, and there is a need to develop in vitro bioassays to reliably test the biological activity of insulin products. This article describes an in vitro cell-based method to assess the biological activity of insulin glargine, insulin aspart, and insulin lispro in a step-by-step manner.

Economic and socioecological perspectives of urban wetland loss and processes: a study from literatures.

Existing literatures across the world highlighted the causes and rate of wetland loss; however, so far, no researches tried to analyze how these are guided by the socioeconomic and ecological conditions. The current review work wished to explore how economic and socioecological perspectives could control the rate and drivers of urban wetland loss. Through meta-analysis, this study also intended to explore the changing polarity in research publication and collaborative research. Total 287 original research articles indicating the rates and drivers of wetland loss from 1990 to June 2022 for the first objective and 1500 articles focusing wetland researches from Dimensions AI database for the last objective were taken.Results clearly revealed that the rate of urban wetland loss varies from 0.03 to 3.13% annually, and three main drivers like built-up, agricultural expansions, pollution were identified all across the world. Loss rate was found maximum in the developing and least developed countries. Pollution, built-up expansion, and agriculture expansion, respectively, in developed, developing, and least developed nations were identified as the most dominant drivers of urban wetland loss. Linking loss rate and drivers with socioecological and economic perspectives revealed that human development index (HDI), ecological performance index (EPI), sustainable development goal index (SDGI), and social progress index (SPI) is negatively associated with the rate of urban wetland loss. Contrarily, a poverty rate encouraged higher rate of loss. This study articulated that improving these socioecological and economic conditions could help wetland conservation and restoration to achieve SDGs.

Transfer-recursive-ensemble learning for multi-day COVID-19 prediction in India using recurrent neural networks.

The COVID-19 pandemic has put a huge challenge on the Indian health infrastructure. With a larger number of people getting affected during the second wave, hospitals were overburdened, running out of supplies and oxygen. Hence, predicting new COVID-19 cases, new deaths, and total active cases multiple days in advance can aid better utilization of scarce medical resources and prudent pandemic-related decision-making. The proposed method uses gated recurrent unit networks as the main predicting model. A study is conducted by building four models pre-trained on COVID-19 data from four different countries (United States of America, Brazil, Spain, and Bangladesh) and fine-tuned on India's data. Since the four countries chosen have experienced different types of infection curves, the pre-training provides a transfer learning to the models incorporating diverse situations into account. Each of the four models then gives 7-day ahead predictions using the recursive learning method for the Indian test data. The final prediction comes from an ensemble of the predictions of the different models. This method with two countries, Spain and Bangladesh, is seen to achieve the best performance amongst all the combinations as well as compared to other traditional regression models.