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BackgroundPrevious studies have found an association between early entry to childcare and risk for overweight and obesity at 3 years of age. These studies, however, have been conducted primarily with higher income White populations or have found increased risk in the children of educated mothers.ObjectiveTo assess the relationship between timing of entry to childcare and duration of childcare and pediatric overweight and obesity in a high risk population.MethodsUsing data from a longitudinal cohort of low-income Latino children in San Francisco, we evaluated the association between time of entry to childcare, hours in childcare, and risk for overweight and obesity at age 4. Similarly, we evaluated the relationship between these same childcare parameters and body mass index Z score and risk of having a waist circumference (WC) percentile ≥90th at 4 years of age.ResultsIn contrast with previous studies, we found no association between being in childcare at 4 years of age or number of hours per week in childcare and risk for childhood overweight, obesity or WC ≥90th percentile at age 4. Additionally, we found no association between age of entry to childcare (≤6 months or ≤12 months of age) with risk for overweight or obesity at age 4. Future studies need to further evaluate the differential impact of childcare on early childhood obesity in relation to race/ethnicity and lower socioeconomic status.ConclusionLow-income children may not be at increased risk for obesity in relation to early childcare exposure.

Abstract We introduce an impact‐based framework to evaluate seasonal forecast model skill in capturing extreme weather and climate events over regions prone to natural disasters such as floods and wildfires. Forecasting hydroclimatic extremes holds significant importance in an era of increasing hazards such as wildfires, floods, and droughts. We evaluate the performance of five Copernicus Climate Change Service (C3S) seasonal forecast models (CMCC, DWD, ECCC, UK‐Met, and Météo‐France) in predicting extreme precipitation events from 1993 to 2016 using 14 indices reflecting timing and intensity (using absolute and locally defined thresholds) of precipitation at a seasonal timescale. Performance metrics, including Percent Bias, Kendall Tau Rank Correlation Score, and models' discrimination capacity, are used for skill evaluation. Our findings indicate that the performance of models varies markedly across regions and seasons. While models generally show good skill in the tropical regions, their skill in extra‐tropical regions is markedly lower. Elevated precipitation thresholds (i.e., higher intensity indices) correlate with heightened model biases, indicating deficiencies in modeling severe precipitation events. Our analysis using an impact‐based framework highlights the superior predictive capabilities of the UK‐Met and Météo‐France models in capturing the underlying processes that drive precipitation events, or lack thereof, across many regions and seasons. Other models exhibit strong performance in specific regions and/or seasons, but not globally. These results advance our understanding of an impact‐based framework in capturing a broad spectrum of extreme weather and climatic events, and inform strategic amalgamation of diverse models across different regions and seasons, thereby offering valuable insights for disaster management and risk analysis.

The Islamic heritage constitutes a very precious treasure in Algeria, especially the places of worship (mosques), which reflect the symbol of this heritage. They are considered important landmarks in cities through architectural elements such as the dome and the minaret. Minarets are used by the muezzin to invite people to pray; they were previously built near the mosque or inside it, next to the prayer room. Later, they appeared as angular towers of mausoleums. This research is part of an analytical study of the minarets in Algeria during the medieval period (Bani Hamad, Moravid, Zayyanid, Marinid, and Ottoman) which were selected and then classified according to their various typologies (dimensions, forms, designs, etc.), and evolution over time. The main objectives of this work are to search for the forms that determine the typology of the minarets of each period. It also examines the correlation between dimensions and geometric parameters employed in the design conception of these minarets. The research followed a monographic method that relies on field observation and documentation, while including a thorough reading of history. The results show that the constant form of the vertical section of the minaret, with the same dimensions between the top and bottom, represents two-thirds of the main tower of the minarets. We also conclude that the square shape of the horizontal section of the minaret represents two-thirds of the main tower of the minarets, which expresses the most earthquake-resistant form. These dimensions play a pivotal role in enhancing the minaret's visual allure and architectural equilibrium, in addition to their earthquake resistance virtues.

Human activities and natural phenomena continually transform the Earth’s surface, presenting ongoing challenges to the environment. Therefore, the accurate and timely monitoring and prediction of these alterations are essential for devising effective solutions and mitigating environmental impacts in advance. This study introduces a novel framework, called HCD-Net, for detecting changes using bi-temporal hyperspectral images. HCD-Net is built upon a dual-stream deep feature extraction process, complemented by an attention mechanism. The first stream employs 3D convolution layers and 3D Squeeze-and-Excitation (SE) blocks to extract deep features, while the second stream utilizes 2D convolution and 2D SE blocks for the same purpose. The deep features from both streams are then concatenated and processed through dense layers for decision-making. The performance of HCD-Net is evaluated against existing state-of-the-art change detection methods. For this purpose, the bi-temporal Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) hyperspectral dataset was utilized to assess the change detection performance. The findings indicate that HCD-Net achieves superior accuracy and the lowest false alarm rate among the compared methods, with an overall classification accuracy exceeding 96%, and a kappa coefficient greater than 0.9.

Streamflow predictions are vital for detecting flood and drought events. Such predictions are even more critical to Sub-Saharan African regions that are vulnerable to the increasing frequency and intensity of such events. These regions are sparsely gaged, with few available gaging stations that are often plagued with missing data due to various causes, such as harsh environmental conditions and constrained operational resources. This work presents a novel workflow for predicting streamflow in the presence of missing gage observations. We leverage bias correction of the Group on Earth Observations Global Water and Sustainability Initiative ECMWF streamflow service (GESS) forecasts for missing data imputation and predict future streamflow using the state-of-the-art temporal fusion transformers (TFTs) at 10 river gaging stations in the Benin Republic. We show by simulating missingness in a testing period that GESS forecasts have a significant bias that results in poor imputation performance over the 10 Beninese stations. Our findings suggest that overall bias correction by Elastic Net and Gaussian Process regression achieves superior performance relative to traditional imputation by established methods. We also show that the TFT yields high predictive skill and further provides explanations for predictions through the weights of its attention mechanism. The findings of this work provide a basis for integrating Global streamflow prediction model data and the state-of-the-art machine learning models into operational early-warning decision-making systems in resource-constrained countries vulnerable to drought and flooding due to extreme weather events.

Several drought indices have been developed based on various processes (e.g., precipitation, soil moisture, vegetation health) that respond differently to modes of climate variability, shadowing their relatability to teleconnections, which in turn, limits drought forecasting. In this study, we advanced the multivariate analysis of droughts by using long-term Terrestrial Water Storage estimates, soil moisture and precipitation data along with normalized difference vegetation index. To this end, we employed a Vine copula approach using Archimedean and Elliptical copula families to generate two novel multivariate drought indices called Combined Standardized Drought Index (CSDI), based on agricultural, meteorological, hydrological and ecological univariate indices (i.e., the Eco-meteo-hydrologic index and the Agro-meteo-hydrologic index) for 33 major river basins across the globe between 1982 and 2015. To overcome the challenges associated with vine copula building blocks, we exhausted the possible choices of vine trees and selected the superior model based on a variety of performance metrics. CSDIs showed an integrated representation of univariate drought indices and revealed a more comprehensive and improved picture of intensity, duration and frequency of droughts. Our composite analysis showed that El Niño and La Niña have a significant impact on the regional drought occurrences across the globe, with highest impacts observed for fall. Results also showed that CSDIs can extract more conclusive anomalies in response to ENSO signals than univariate indices, as they better represent the ecosystem response to teleconnections.

Information about soil consolidation is essential in geotechnical design. Because of the time and expense involved in performing consolidation tests, equations are required to estimate compression index from soil index properties. Although many empirical equations concerning soil properties have been proposed, such equations may not be appropriate for local situations. The aim of this study is to investigate the consolidation and physical properties of the cohesive soil. Artificial Neural Network (ANN) has been adapted in this investigation to predict the compression index and compression ratio using basic index properties. One hundred and ninety five consolidation results for soils tested at different construction sites in Baghdad city were used. 70% of these results were used to train the prediction ANN models and the rest were equally divided to test and validate the ANN models. The performance of the developed models was examined using the correlation coefficient R. The final models have demonstrated that the ANN has capability for acceptable prediction of compression index and compression ratio. Two equations were proposed to estimate compression index using the connecting weights algorithm, and good agreements with test results were achieved.

Two types of polymers (plastomer (functionalized polyethylene (PE)) and elastomer (styrene-butadiene-styrene (SBS))) were used for shifting up asphalt binder performance grade (PG) and tensile strength resistance (moisture damage) of the asphalt concrete mixture. It is found that adding 3.5% functionalized polyethylene (PE) polymer to the binder is more effective than adding 4% styrene-butadiene-styrene (SBS) to shift up asphalt PG by two grades to PG 76-16. Furthermore, the viscosity of the binder increased about 200% when using 4% SBS, while there is no significant effect on viscosity when 3.5% PE is used. Therefore, there is no need to increase the temperature of mixing and compaction which may affect polymers. The indirect tensile test was used for measuring tensile strength ratio of dry and wet samples (conditioned according to ASTM D4867) and found that this ratio increased by 10 to 18% when using 4% SBS and 3.5% PE, respectively. Fracture energy (area under the strength-strain curve) and elasticity were estimated for neat and modified mixture samples.

This paper studies the effect of different design spectral response acceleration parameters as suggested by the uniform building code (UBC), unified facilities criteria (UFC), and Iraqi seismic code(1997) (ISC 97) on the seismic response of reinforced concrete multi-story framed building located in Baghdad city, Iraq. These parameters are: (a) spectral response accelerations Ss, at short periods, and S1 at a 1-second period in accordance with international building code (IBC), (b) seismic zone factor (Z) according to UBC, (c) Seismic hazard zoning coefficient (Z) according to ISC 97. In this paper, first, the elastic seismic responses for significant modes of vibration for chosen building under design response spectrum that obtained from the above mentioned codes are calculated, and then a comparison was made among different design spectral response acceleration parameters. The intent of this study is to review the seismic provisions of the current edition of Iraqi seismic code (1997) to determine whether it provides an equivalent level of safety to that contained in other international codes. Design base shears, lateral seismic forces, inter story drifts, response spectrum modal, effective seismic modification, floors acceleration and story shears are comparatively presented.

Owing to clinical success of immune-checkpoint blockade, immunotherapy is becoming a cornerstone of modern oncology, and immuno-oncology is at the forefront of basic cancer research. This commentary outlines future opportunities for immuno-oncology modeling., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Triple-negative breast cancers (TNBCs) are associated with poor survival mediated by treatment resistance. TNBCs are fibrotic, yet little is known regarding how the extracellular matrix (ECM) evolves following therapy and whether it impacts treatment response. Analysis revealed that while primary untreated TNBCs are surrounded by a rigid stromal microenvironment, chemotherapy-resistant residual tumors inhabit a softer niche. TNBC organoid cultures and xenograft studies showed that organoids interacting with soft ECM exhibit striking resistance to chemotherapy, ionizing radiation, and death receptor ligand TRAIL. A stiff ECM enhanced proapoptotic JNK activity to sensitize cells to treatment, whereas a soft ECM promoted treatment resistance by elevating NF-κB activity and compromising JNK activity. Treatment-resistant residual TNBCs residing within soft stroma had elevated activated NF-κB levels, and disengaging NF-κB activity sensitized tumors in a soft matrix to therapy. Thus, the biophysical properties of the ECM modify treatment response, and agents that modulate stiffness-dependent NF-κB or JNK activity could enhance therapeutic efficacy in patients with TNBC., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2021 Drain et al.)

Steroids remain an essential part of immunosuppressive therapy for renal transplant patients since the start of transplant era. Different immunosuppressive regimens are prescribed so as to minimize the side effects. The purpose of our study is to compare the outcome of early steroid withdrawal with steroid maintenance protocol. It is a prospective nonrandomized study. All patients that received renal transplants from January 2011 to December 2013 were included in the study. Early steroid withdrawal at day 5 was done in low immunological risk patients, and the results were compared with the steroid maintenance group, at one-year, posttransplant. Outcome measures included acute rejection (AR), slow graft function and delayed graft function (SGF and DGF), patient and graft survival, and new-onset diabetes after transplant (NODAT), dyslipidemia, hypertension, and obesity. A total of 249 patients were divided into two groups - 105 patients had early steroid withdrawal and 144 patients were maintained on steroid therapy. Outcome measures were compared one-year posttransplant. There was no significant difference in AR, patient and graft survival, creatinine level, and weight gain. However, a significant difference in systolic and diastolic blood pressure, lipid profile, NODAT, SGF, and DGF was found in the steroid group. Our study shows that early steroid withdrawal is a safe standard of care in low immunological risk patients.

Human hepatocellular carcinoma is one of the most common recurrent malignancies since there is no effective therapy for it. Silibinin, a widely used drug and supplement for various liver disorders, demonstrated anti-cancer effects on human hepatocellular carcinoma, human prostate adenocarcinoma cells, human breast carcinoma cells, human ectocervical carcinoma cells, and human colon cancer cells. Considering the anti-hepatotoxic activity of silibinin and its strong preventive and anti-cancer efficacy against various epithelial cancers, we investigated the efficacy of silibinin against human HCC and HUVEC cell lines. Silibinin effects on the growth and mode of cell death of these two cell lines are presented in this paper. HepG2 and HUVEC cells were incubated with different doses of silibinin (12.5, 25, 50, 100, 150 and 200 μg/mL) at 24, 48, and 72 h. Cytotoxicity was assessed using MTT and Trypan blue assays. Mode of cell death induced by silibinin was investigated using LDH assay and acridine orange/PI double dye staining. The results showed that silibinin has dose-dependent inhibitory effect on the viability of HepG2 and HUVEC cells. However, Silibinin causes a more continuous dose-dependent cytotoxicity in HepG2 cells compared to the HUVEC cells in which some degrees of resistance is apparent at the beginning. The mode of cell death looks also different in these two cell lines with HepG2 cells being more in favor of apoptosis while necrosis is more evident for the HUVEC cells.

Objectives: The primary objective was to determine the association between histopathological and microbiological findings in patients clinically suspected to have tuberculous lymphadenitis. A secondary objective was to assess the diagnostic utility of GeneXpert in lymph node specimens., Method: This was a single-centre prospective cohort study, performed in the Infectious Disease Clinic at The Indus Hospital. Three hundred and forty-one adult patients with chronically enlarged, accessible lymph nodes were enrolled after obtaining verbal consent, between February 2013 and April 2016. Tissue specimens were processed for histopathology, acid-fast bacillus (AFB) microscopy, AFB culture, and GeneXpert. Based on these results, anti-tuberculosis therapy (ATT) was prescribed. Clinical characteristics and treatment outcomes were recorded., Results: There were 297 evaluable patients; 74.4% were diagnosed with tuberculous lymphadenitis (TBLA), 6.7% with a malignancy, and 12.8% with reactive nodes. TBLA was diagnosed on suggestive histopathology in 89.6% of cases, followed by GeneXpert (32.6%), mycobacterial culture (26.6%), and AFB smear positivity (12.5%). The sensitivity of GeneXpert was 65.7% when assessed against AFB culture. Drug resistance was displayed by 8.2% of GeneXpert-positive cases and 11.7% of culture-positive cases. The majority of TBLA patients (88.7%) responded favorably to ATT., Conclusions: In light of laboratory evidence, a quarter of patients suspected of TBLA had an alternative diagnosis, highlighting its importance in avoiding over-treatment and diagnostic delays in malignancy. Although sensitivity is poor, the demonstration of drug resistance by both GeneXpert and AFB culture represents a useful tool to guide treatment., (Copyright © 2018. Published by Elsevier Ltd.)

Low glucose condition induces neuronal cell-death via intracellular mechanisms including mitogen-activated protein kinases (MAPK) signaling pathways. It has been shown that low glucose medium decreases neuronal survival in cerebellar granule neurons (CGNs). In this study, we have examined the activation of JNK, p38kinase and ERK1/2 pathways in low glucose medium in CGNs. The CGNs were prepared from new-born (P-2 and P-5) rats and cultured in Dulbecco's Modified Eagle's Medium high (DMEM-HIGH) glucose supplemented with Fetal Bovine Serum (FBS) 10% for 7 days. The glucose deprivation was induced through replacing the culture medium with the low glucose (5 mM) medium. The MAPK pathways activation was evaluated through phospho specific antibodies using western blot. The viability of cells was measuring using MTT assay. The results indicated that low glucose reduces the cell survival and brain-derived neurotrophic factor (BDNF) elevates the cell viability in CGNs. The basal c-Jun N-terminal kinase (JNK) activity was high in CGNs and glucose deprivation for 24 h had increased phospho-JNK level to 2-fold compared to basal. BDNF treatment reduced the basal JNK activity within 30 min but had no effect in longer incubations. BDNF also blocked the low glucose-induced JNK activation. In addition, CGNs exhibited high p38 phosphorylation in low glucose medium in 48 h. These results demonstrated that in sustained low glucose conditions, CGNs had high activity of stress-activated MAPK which could induce cellular damage. Moreover, BDNF can prevent JNK and p38 activation in stress conditions and increase cell viability. Our results suggest that in sustained stress conditions, inhibition of JNK and/or p38 pathways might protect neurons from damage in low glucose conditions.

Yersinia enterocolitica (Ye) targets mouse dendritic cells (DCs) and inhibits their ability to trigger T cell activation. Here we have investigated whether Ye might interfere with antigen presentation in DCs. Infection of DCs with the Ye wild-type strain reduced OVA uptake by DCs as demonstrated by flow cytometry and confocal laser scan microscopy. In contrast, DCs infected with Yersinia outer protein P (YopP)-deficient mutant strain rapidly internalized OVA. Furthermore, transfection of DCs with YopP, but not with a cysteine protease deficient YopP-C172A mutant, reduced uptake of OVA. This finding suggests that YopP, a virulence factor of Ye, inhibits OVA uptake by DCs. By the use of MAPK inhibitors we provide evidence that YopP mediates reduction of OVA uptake by its ability to block MAPK signalling pathways in host cells. Using transferrin (Tf) as specific marker for clathrin-mediated endocytosis (CME) and lucifer yellow (LY) as specific marker for macropinocytosis (MP) we could show that YopP inhibits CME, whereas other Yops inhibit MP. In keeping with these data, activation and proliferation of OVA-specific T cells was reduced when DCs were treated with MAPK inhibitors. Together, our data demonstrate that (i) MAPK play an important role in antigen uptake by CME in DCs, and (ii) that YopP inhibits this pathway of antigen uptake in DCs, which might contribute to evasion of adaptive immunity.

Tumors are stiffer than normal tissue, and tumors have altered integrins. Because integrins are mechanotransducers that regulate cell fate, we asked whether tissue stiffness could promote malignant behavior by modulating integrins. We found that tumors are rigid because they have a stiff stroma and elevated Rho-dependent cytoskeletal tension that drives focal adhesions, disrupts adherens junctions, perturbs tissue polarity, enhances growth, and hinders lumen formation. Matrix stiffness perturbs epithelial morphogenesis by clustering integrins to enhance ERK activation and increase ROCK-generated contractility and focal adhesions. Contractile, EGF-transformed epithelia with elevated ERK and Rho activity could be phenotypically reverted to tissues lacking focal adhesions if Rho-generated contractility or ERK activity was decreased. Thus, ERK and Rho constitute part of an integrated mechanoregulatory circuit linking matrix stiffness to cytoskeletal tension through integrins to regulate tissue phenotype.

Tissue development, homeostasis and tumor pathogenesis all depend upon a complex dialogue between multiple cell types operating within a dynamic three-dimensional (3D) tissue extracellular matrix microenvironment. A major issue is whether the spatial organization of a cell within this 3D tissue microenvironment could modulate cell responsiveness to regulate cell fate decisions such as survival, and if so how. Classic developmental model systems and transgenic animals are instructive but pose special challenges for investigators conducting signaling studies and biochemical assays in tissues. As an alternative, 3D culture model systems exist in which cell-adhesion dependent tissue architecture, heterotypic cell-cell interactions and tissue differentiation can be recapitulated with good fidelity. 3D cell culture models are slowly revealing how tissue architecture can dramatically influence how a cell responds to exogenous stimuli to modify its apoptotic behavior and hence should prove instrumental for identifying novel cell death pathways.

Invasive carcinomas survive and evade apoptosis despite the absence of an exogenous basement membrane. How epithelial tumors acquire anchorage independence for survival remains poorly defined. Epithelial tumors often secrete abundant amounts of the extracellular matrix protein laminin 5 (LM-5) and frequently express alpha6beta4 integrin. Here, we show that autocrine LM-5 mediates anchorage-independent survival in breast tumors through ligation of a wild-type, but not a cytoplasmic tail-truncated alpha6beta4 integrin. alpha6beta4 integrin does not mediate tumor survival through activation of ERK or AKT. Instead, the cytoplasmic tail of beta4 integrin is necessary for basal and epidermal growth factor-induced RAC activity, and RAC mediates tumor survival. Indeed, a constitutively active RAC sustains the viability of mammary tumors lacking functional beta1 and beta4 integrin through activation of NFkappaB, and overexpression of NFkappaB p65 mediates anchorage-independent survival of nonmalignant mammary epithelial cells. Therefore, epithelial tumors could survive in the absence of exogenous basement membrane through autocrine LM-5-alpha6beta4 integrin-RAC-NFkappaB signaling.