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Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

Abstract Osmotic stress is one of the main destructive abiotic factors that hinder plant growth and development. In this research, the role of silver nanoparticles (Ag NPs) in mitigating the negative impact of osmotic stress on in vitro grown Chenopodium quinoa (Quinoa 6 Line; Q6) was investigated to determine whether Ag NPs were able to reduce the negative effects on the in vitro grown cultures of the Q6 line. The explants were subcultured onto a special osmostressing media containing sucrose, sorbitol, or mannitol at different levels (0.1, 0.2, 0.3, and 0.4 mol/L) to mimic the osmotic stressing environment for four weeks. Then, stress physiological responses of in vitro grown Q6 under the induced osmotic stress were investigated to determine the highest stress level that the microshoots could tolerate. Next, Ag NPs; 25, 50, and 75 mg/L were added to the medium that contained the highest stress level of the induced osmotic stress to determine if their addition improved the physiological performance of the Q6 microshoots under the most severe osmotic agent levels. The results revealed that 0.4 mol/L sucrose, 0.3 mol/L sorbitol, and 0.3 mol/L mannitol were the highest stress levels that the microshoots could tolerate. The addition of 75 mg/L Ag NPs to the previous highest stress levels resulted in a significant increase in the following: stem length (SL), leaves number (LN), fresh weight (FW), dry weight (DW), total chlorophyll, protein, calcium (Ca), and phosphorus (P) contents, while it caused a reduction in proline, sodium (Na) ions, and potassium (K) ions. These results indicate that the negative consequences of osmotic stress on Q6 quinoa microshoots could be mitigated by adding specific concentrations of Ag NPs to the culture medium.

IntroductionThis study addresses the rising cardiovascular disease (CVD) rates in the United Arab Emirates (UAE) by investigating the occurrence and impact of genetic variants in CVD-related genes.MethodsWe collected all genes linked to heritable CVD from public and diagnostic databases and mapped them to their corresponding biological processes and molecular pathways. We then evaluated the types and burden of genetic variants within these genes in 343 individuals from the Emirati Mendelian Study Cohort and 3,007 national electronic health records.ResultsWe identified a total of 735 genes associated with heritable CVD, covering a range of cardiovascular conditions. Enrichment analysis revealed key biological processes and pathways, including Apelin, FoxO, and Ras signaling, that are implicated across all forms of heritable CVD. Analysis of a UAE cohort of 3,350 individuals showed a predominance of rare and unique CVD variants specific to the population. The study found a significant burden of pathogenic variants in families with CVD within the Emirati Mendelian cohort and re-assessed the pathogenicity of 693 variants from national health records, leading to the discovery of new CVD-causing variants.DiscussionThis study underscores the importance of continuously updating our understanding of genes and pathways related to CVD. It also highlights the significant underrepresentation of the UAE population in public databases and clinical literature on CVD genetics, offering valuable insights that can inform future research and intervention strategies.

A stable dividend policy is often in the best interests of both the company and its shareholders. Considering the importance of dividend policy, we examine the determinants of dividend payment in Malaysian Sharia-compliant listed firms and the moderating role of board directors. To this end, we apply a static-panel model using data of Malaysian Shariah-compliant listed firms from 2014 to 2020. We find that ROA (Return on Asset) and Price-Earnings ratio (PER) have a significant positive impact on the dividend payout ratio (DPR). On the other hand, NAV (Net Asset Value) shows a negative and significant relationship with the DPR. Our findings also reveal that the board of directors significantly and positively influence the decision to pay dividends. The findings of the study hold significant importance for corporations in determining a suitable dividend policy that can ensure the sustainability of a consistent dividend payout and ensure their organization's financial stability, particularly in Malaysian-listed Shariah-compliant firms.

Dendritic cells (DCs) play an important role in the formation of the immune response, and they are involved in the pathogenesis of autoimmune diseases. Targeting DCs has thus emerged as a new therapeutic modality in the management of inflammatory and autoimmune diseases. DCs can be manipulated ex vivo and then injected back into humans to suppress the immune response. They can also be manipulated in vivo by delivering specific molecules into the DCs. Co-stimulatory molecules that shape DCs interaction with T cells can also be targeted to suppress immunity. This review tackles the latest advances in each of the 3 presented approaches.

Abstract Viral infections remain a major risk in immunocompromised pediatric patients, and virus-specific T cell (VST) therapy has been successful for treatment of refractory viral infections in prior studies. We performed a phase II multicenter study (NCT03475212) for the treatment of pediatric patients with inborn errors of immunity and/or post allogeneic hematopoietic stem cell transplant with refractory viral infections using partially-HLA matched VSTs targeting cytomegalovirus, Epstein-Barr virus, or adenovirus. Primary endpoints were feasibility, safety, and clinical responses (>1 log reduction in viremia at 28 days). Secondary endpoints were reconstitution of antiviral immunity and persistence of the infused VSTs. Suitable VST products were identified for 75 of 77 clinical queries. Clinical responses were achieved in 29 of 47 (62%) of patients post-HSCT including 73% of patients evaluable at 1-month post-infusion, meeting the primary efficacy endpoint (>52%). Secondary graft rejection occurred in one child following VST infusion as described in a companion article. Corticosteroids, graft-versus-host disease, transplant-associated thrombotic microangiopathy, and eculizumab treatment correlated with poor response, while uptrending absolute lymphocyte and CD8 T cell counts correlated with good response. This study highlights key clinical factors that impact response to VSTs and demonstrates the feasibility and efficacy of this therapy in pediatric HSCT.

AbstractThis study addresses Bangladesh’s unemployment problem and its youth’s limited entrepreneurial aspiration focusing on critical factors that influence entrepreneurial intentions among university students in Bangladesh. Recognizing universities’ role in fostering entrepreneurship, the study aims to identify these determinants, bridging a gap in literature in the context of Bangladesh. Built upon an extended theory of planned behavior, the study incorporates ‘access to finance’ and ‘entrepreneurship program’ as mediators. This framework examines the relationships of ‘attitude’, ‘subjective norms’, ‘perceived behavioral control’, ‘entrepreneurship program’, ‘access to finance’, and their collective impact on entrepreneurial intentions. Utilizing stratified random sampling, the researchers collected data from 394 students across 23 selected Bangladeshi universities offering entrepreneurship programs encompassing Faculty of Business & Entrepreneurship and Faculty of Science & Engineering. The study employed Structural equation modeling (SEM) for analyzing the data. The findings revealed that there were positive relationships between ‘entrepreneurial intention’ and ‘attitude’, ‘subjective norms’, ‘perceived behavioral control’, ‘entrepreneurship program’, and ‘access to finance’. The findings have practical implications for Bangladesh’s government and educational institutes when it comes to promoting entrepreneurship programs extensively. The empirical results clearly demonstrate that the integration of access to finance and practical entrepreneurship programs significantly boosts the entrepreneurial aspirations of university students, encouraging them to pursue entrepreneurship as a career path. This, in turn, contributes to the advancement of economic sustainability in Bangladesh. These outcomes are consistent with the overarching aims of Sustainable Development Goal 8, which strives to foster continuous economic growth, generate employment prospects, and ensure decent work opportunities, particularly for the youth.

BackgroundReproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER)-positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.MethodsAnalyses included up to 23 353 cases and 71 072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative breast cancer) and by invasiveness. All statistical tests were 2-sided.ResultsCompared with nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like, and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46 for multiparous women with luminal A-like tumors 20 to less than 25 years after last birth and 45 to less than 50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95% CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95% CI = 0.79 to 1.34, for multiparous women 25 to less than 30 years after last birth). Older age at first birth (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) and breastfeeding (Pheterogeneity < .001 for triple-negative compared with luminal A-like breast cancer) were associated with lower risk of triple-negative breast cancer but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.ConclusionsThis large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared with other subtypes, with implications for the understanding of disease etiology and risk prediction.

Abstract Date palm (Phoenix dactylifera( cv. Medjool is a significant plant, grown in Jordan. In vitro propagation gives operative resources for the significant propagation of date palms. Maximum callus induction was achieved from MS media supplemented with benzyl amino purine (BA) and naphthalene acetic acid (NAA). The highest plant regeneration was recorded on MS medium supplemented with dichlorophenoxyacetic acid (2,4-D) at 3.0 mg/L, and BA at 2.0 mg/L. A significant positive impact on shoot formation was recorded on MS medium supplemented with 1.0 mg/L BA with 0.5 to 1.5 mg/L NAA in both liquid and solid MS medium. To maintain survival and regrowth capacity, sucrose could be used for medium-term conservation at lower concentrations (0.1 - 0.2 M). In addition, sorbitol might be used at 0.1 M to maintain the quality of explants. The vitrification technique for long-term preservation was experimented. Embryogenic callus was used as explants for conservation. The survival as well as regrowth percentages of non-cryopreserved and cryopreserved tissue cultures were affected by their duration of treatment with the vitrification solution plant vitrification solution 2 (PVS2) and modified plant vitrification solution 2 (MPVS2). Results showed that using PVS2 for 60 minutes for cryopreserved calli was more effective than other treatments. After storage in liquid nitrogen, the highest survival rate (65%) and regrowth rate (40%) were achieved.

BackgroundPredict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).MethodThe prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.ResultsHaving a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0.902 for patients with ER-positive tumours (p = 2.3 × 10-6) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.ConclusionThe inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predictions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration.

One of the primary issues with processed foods during heat treatment and freezing storage is fat oxidation, which causes significant changes in fats due to their interaction with reactive oxygen species (ROS). This interaction leads to the creation of various aldehydes that have a high affinity for large molecules, such as proteins, leading to the formation of final products of advanced oxidation processes that contribute to food spoilage. Co-oxidation can also result in extensive damage. Another problem affecting the quality and nutritional value of meat products is protein oxidation, which can occur during storage via freezing and thawing or as a result of heat treatment. Heat treatment can cause physical and chemical changes, such as the loss of some essential amino acids and the transformation of certain amino acids into carbonyl compounds via various mechanisms. Protein oxidation is indicated by the accumulation of these carbonyl compounds, and the heat treatment can lead to the denaturation of myoglobin, which is responsible for the brown color of cooked meat and is influenced by several factors. Active protein aggregates can interact with the oxidation products of polyunsaturated fatty acids and with carbohydrate glycation or glycoxidation to produce Maillard products. It is critical to understand the oxidative changes that occur in fats and proteins in food, particularly in meat products, since these components are among the primary constituents of food.

Implant-supported immediate loading full-arch rehabilitation has been documented in the literature. More recently, computed surgical guides have frequently been used since they facilitate planning and performing surgical treatment without the need to raise a flap, thus reducing trauma and morbidity. This case report describes an immediate full-arch, fixed rehabilitation with full loading placed on four commercially available 3D-printed implants, with a 24-month follow-up. The implants were placed with the help of a digitally planned 3D-printed surgical guide. The provisional fixed prosthesis installed immediately was replaced after 3 months. At the time, the soft and hard tissue around the implants appeared stable, without signs of inflammation. The same situation was observed at the 24-month follow-up. Three-dimensional-printed implants seem to be a promising choice in this case. However, further clinical studies with longer follow-up periods are necessary to confirm their efficacy.

Caper (Capparis spinosa L.) is a medical plant grown in Jordan. Mass harvesting of caper plants from their origin environments caused a reduction of these germplasm. Therefore, an easy and consistent method for clonal proliferation and callus induction was established for this species. C. spinosa L. in vitro culture affected in MS medium provided by 0.5 mg/L BAP gave 5.9 microshoots/explant. Two months later MS medium supplemented with 2.0 mg/L NAA developed a maximum callus induction of 33.1 mm. Ex vitro, in vitro, and callus growth of C. spinosa L. using ethanolic and methanolic extracts were tested for their antimicrobial activity against different species of bacteria and fungi. Both ex-vitro and in vitro plants exhibited similar antimicrobial activity. Maximum ex vitro plant antibacterial activity was (23 mm ± 0.58 inhibition zone) against Staphylococcus epidermidi. In comparison, callus extracts gave the highest antibacterial activity against Bacillus cereus and Escherichia coli. Moreover, caper plant extracts showed different antifungal effects against the tested fungi species. Investigation of the data showed that ex-vitro extract exhibited maximum antifungal activity compared to in vitro plants. Additionally, exposed Bemisia tabaci 4th nymphal instar to C. spinosa L. extracts suffered mortality ranging from 2 to 28%. In most instances, both ethanolic and methanolic extracts affected the survival of B. tabaci more than the control. The current study confirmed that C. spinosa L. has a wide range of antibacterial, antifungal, and insecticidal activity.

This study evaluated β-human chorionic gonadotropin (hCG) changes during the early period of pregnancy in an attempt to predict successful pregnancy outcomes in ART. It determined the median values of the β-hCG and the 2-day β-hCG increments of clinical vs biochemical pregnancies. The results of fresh day 3 embryo, frozen day 3 embryo, and frozen day 5 embryo transfers were evaluated. The cutoff val ues of β-hCG and the 2-day increments predicting clinical pregnancy and delivery were determined. All women who underwent embryo transfer and had a singleton pregnancy from January 2017 to December 2019 were included. As expected, clinical pregnancies had higher initial median β-hCG values compared to biochemical pregnancies (fresh day 3 (400 vs 73 mIU/mL), frozen day 3 (600 vs 268.5 mIU/mL) and frozen day 5 (937 vs 317 mIU/mL)). Nonetheless, the abortion rate was significantly lower in the group with β-hCG above the cutoff values in fresh (141 mIU/mL) and frozen (354.5 mIU/mL) cleavage stage transfers (17.2% vs 44%, P < 0.001 and 18.5% vs 38%, P = 0.003, respectively). Blastocyst transfers resulted in higher median initial β-hCG compared to cleavage embryo transfers (937 vs 600 mIU/mL), and the initial β-hCG values from frozen cleavage embryos were higher compared to fresh cleavage embryos (600 vs 400 mIU/mL). Earlier implantation in frozen cycles may be caused by freezing–thawing procedures. Moreover, in fresh cycles, negative effects of the hormonal milieu of fresh cycles may delay implantation. These results indicate that high initial β-hCG and high 2-day β-hCG increments demonstrated better outcomes, including more clinical pregnancies and fewer abortions.

Disparities in access to water, sanitation, and hygiene within high-income countries are common and often occur across racial/ethnic lines. The Arab-Bedouins in Israel, a formerly nomadic ethno-national minority, have experienced displacement, forced sedentarization, and poverty since Israel was founded. Land disputes with the government have led to precarious living arrangements, including unrecognized villages that the government considers illegal. We administered a structured questionnaire in one government-planned, two legally recognized, and two unrecognized Bedouin communities in the Negev (190 households). Only 44% (95% CI 37%, 51%) of households had access to both safely managed drinking water and sanitation; nationally Israel reports over 99% coverage for each. In one unrecognized village, only 15% of households had access to safely managed water and sanitation, comparable to low-income countries. The overall 1-week prevalence of diarrhea in children under 5 years of age was 22% (95% CI 17%, 27%), with substantial variation between communities. These results highlight that universal access to safely managed drinking water and sanitation remains a relevant goal, not only for low- and middle-income countries but for high-income countries. Bedouin communities in the Negev are a prime example, emphasizing that historic gains in global development have not uniformly reached marginalized groups within high-income countries. HIGHLIGHTS Land rights disputes between the Bedouins and the Israeli government have led to poor access to safely managed water and sanitation.; We found that only 44% of households sampled in five Bedouin localities had access to both a safely managed water source and safely managed sanitation.; In one unrecognized village, access to safely managed water and sanitation was worse than in many of the world's poorest countries.;

Concrete is used globally due to its useful mechanical and durability properties. However, concrete requires a massive amount of cement, which is the second-largest source of carbon emission (5–7% of global CO2 emissions) due to its high energy consumption. The gelatinization effect of corn starch as a binder has been explored in the place of cement in concrete. However, there is a need to optimize the various processing conditions to enhance the material strength of the corn starch-based material known as CoRncrete. Two experiments were conducted to optimize the ratio of sand, starch, water, curing temperatures, and time. The compressive and tensile strength of the CoRncrete samples were analyzed. The results showed that the optimum processing conditions having a sand grain size of 0.250–0.425 mm, a mixture ratio of starch, water, and sand 1:1:5, and curing temperature and time of 110 °C and 24 h can yield a maximum compressive strength up to 18.9 MPa. Statistical analysis revealed that the size of sand grains and curing temperatures had the most significant impact on the material’s strength. Microstructural analysis, employing scanning electron microscopy (SEM) and micro-computed tomography (microCT), unveiled numerous internal pores and cracks within the hardened cubic blocks, which significantly decreased the strength. Consequently, future investigations should concentrate on reducing internal pore spaces and cracks to enhance the durability of CoRncrete.