Mutational spectrum associated with oculocutaneous albinism and Hermansky-Pudlak syndrome in nine Pakistani families.

BACKGROUND: Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition. METHODS: Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software. RESULTS: WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1. CONCLUSIONS: Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.

The incidence of pleural infections in Finland.

BACKGROUND: The incidence of pleural infections appears to be increasing in Western countries for unclear reasons. The aim of the study was to describe the incidence and treatment patterns of pleural infections in Finland over three decades. METHODS: Data regarding each treatment episode for pleural infections in the Finnish special medical care between January 1994 and December 2016 was obtained from a national database and compared to the demographics of Finnish residents obtained from the national census bureau. The annual incidence rates, type of treatment given, as well as the lengths of the hospitalization were analyzed. RESULTS: A total of 28,463 episodes were reported, of which 55% were inpatient episodes. Of these, 76% concerned males, and the median age of patients was 60 (interquartile range 49-70) years. The overall incidence of pleural infections was 23.4 per 100.000 patient-years, with a male-to-female -ratio of 3.3:1. The annual incidence rates increased throughout the study period with an average annual percentage change of +11.4% (95% CI ±7.4%). The highest incidence rates (>200 per 100.000 patient-years) were observed in men aged 80 or more. Altogether 88% of patients were treated conservatively. The proportion of patients treated by mini-invasive surgery significantly increased during study period (0-5.9%, p < 0.001) and was associated with shorter hospitalization (median 6 [interquartile range 4-12] days) than open surgery (median 7 [4.5-13] days) (p < 0.001). CONCLUSION: The incidence of pleural infections has increased significantly over the previous decades in Finland and appears to be higher than previously reported, particularly in elderly men.

The early and long-term occurrence of symptomatic venous thromboembolism after lung cancer surgery without extended thromboprophylaxis-a single center experience with 435 patients.

Background: The incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), after lung cancer resections varies in the literature, and there is limited evidence regarding the optimal duration of thromboprophylaxis. This study aimed at determining the early and long-term occurrence of thromboembolic complications in patients who received in-hospital thromboprophylaxis and underwent resective surgery for lung cancer. Methods: The study included all patients who underwent lung cancer surgery at Tampere University Hospital between 2004 and 2016. Postoperative thromboprophylaxis was administered for the duration of the hospitalization. Data on subsequent episodes of VTE and survival were obtained from national registries. The results were compared to a demographically matched reference population. Results: The study comprised 435 patients and 4,338 individuals in the reference population. The overall occurrence of VTE in patients and the reference group was 0.3% vs. 0.2% at 90 days (P=0.56), 3.5% vs. 0.7% at 1 year (P<0.001), 9.2% vs. 2.2% at 3 years (P<0.001), and 18.7% and 3.9% at 5 years (P<0.001), respectively. The majority of cases represented PE. The overall mortality at 5 years was 44.4% vs. 11.6% (P<0.001). No associations between patient characteristics and the occurrence of VTE during follow-up were detected. Conclusions: Patients undergoing lung cancer surgery and who receive in-hospital medical thromboprophylaxis do not seem to be in high risk for symptomatic VTE during the early postoperative period. However, during long-term follow-up the occurrence of symptomatic VTE was significant.

Nanomaterial-based sensors for microbe detection: a review.

Airborne microorganisms pose a significant health threat, causing various illnesses. Traditional detection methods are often slow and complex. This review highlights the potential of nanomaterial-based biosensors, particularly colorimetric sensors, for rapid and on-site detection of airborne microbes. Colorimetric sensors offer real-time visual detection without complex instrumentation. We explore the integration of these sensors with Lab-on-a-Chip technology using PDMS microfluidics. This review also proposes a novel PDMS-based colorimetric biosensor for real-time detection of airborne microbes. The sensor utilizes a color change phenomenon easily observable with the naked eye, simplifying analysis and potentially enabling point-of-care applications.

Treatment Non-adherence Patterns Among Patients With Mental Illness: A Study From the District Mental Health Care Center in India.

INTRODUCTION: The success of any medical intervention, including mental health treatment, depends largely on patient adherence to the prescribed regimen. In psychiatric illnesses, one of the biggest problems is getting people to adhere to their treatment schedule, representing a treatment gap that increases the burdens of patients, families, communities, and countries. Globally, it has become necessary for community health organizations to actively work towards reducing this gap and treatment non-adherence. Therefore, in this study, we aimed to examine treatment non-adherence patterns among patients with mental illness. MATERIALS AND METHODS: This work used a retrospective study design and consecutive sampling. The data source was secondary data obtained from the healthcare records of patients registered in the outpatient department of the District Mental Health Care Center, India, from January 2022 to December 2022. RESULTS: Out of a total of 883 patients recruited for the study, 35.7% (n=315) were on regular follow-up over a duration of more than one year. Among patients with severe mental illness, 46% (n=46) had regular follow-ups and were compliant with therapy. About 49% of patients (n=433) discontinued their treatment after the initial contact with the therapist, with the highest rate among those with substance use disorders (77.0%; n=57). The remaining 15.3% (n=135) of recruited patients discontinued their follow-up appointments over a duration of 1 week to 12 months. Overall, 64.3% (n=568) of the recruited patients discontinued their treatment within one year. CONCLUSION: There was considerable early treatment dropout among patients with mental illness. However, this treatment discontinuation can be avoided because the individual identities of these patients are well-known to the therapist or facility, as they have had at least one interaction with the therapist. In order to improve treatment adherence, patients with mental illnesses must receive consistent support through community outreach programs, home visits, and new strategies to promote treatment compliance.

The Prevention of Seroma Formation Following Modified Radical Mastectomy by Intravenous Hydrocortisone Injection.

Introduction Seroma formation is the most common complication after modified radical mastectomy (MRM). It leads to increased pain and discomfort, potentially prolonging morbidity and treatment. Various treatment modalities are being used to decrease the incidence of seroma formation. The objective of this study was to compare intravenous hydrocortisone injection versus placebo in patients undergoing MRM in terms of frequency of post-operative seroma formation. Methods This randomized, double-blinded, placebo-controlled study was conducted at Surgical Unit-I, Holy Family Hospital, Rawalpindi, Pakistan from January 2021 to December 2021. A total of 152 female patients were randomly assigned to each of the study and placebo groups. Group I patients received 100 mg of hydrocortisone intravenously while group II patients received one ml of 0.9% normal saline intravenously prior to induction of general anesthesia for MRM. The incidence of seroma formation after 10 days of MRM and total drain volume till their removal was measured in all patients. Results The mean age was 48.42±10.15 in Group I, while it was 47.67±10.75 in Group II. Mean drain output till removal was 99.14±31.01 ml in the hydrocortisone group and 177.57±63.37 ml in the placebo group. Forty-eight patients developed seroma (31.58%), of whom nine received intravenous hydrocortisone and 39 received normal saline (P=0.000). Conclusion Intravenous hydrocortisone is effective in terms of frequency of post-operative seroma formation as compared to placebo in patients undergoing MRM.

Internet of Vehicles (IoV)-Based Task Scheduling Approach Using Fuzzy Logic Technique in Fog Computing Enables Vehicular Ad Hoc Network (VANET).

The intelligent transportation system (ITS) relies heavily on the vehicular ad hoc network (VANET) and the internet of vehicles (IoVs), which combine cloud and fog to improve task processing capabilities. As a cloud extension, the fog processes' infrastructure is close to VANET, fostering an environment favorable to smart cars with IT equipment and effective task management oversight. Vehicle processing power, bandwidth, time, and high-speed mobility are all limited in VANET. It is critical to satisfy the vehicles' requirements for minimal latency and fast reaction times while offloading duties to the fog layer. We proposed a fuzzy logic-based task scheduling system in VANET to minimize latency and improve the enhanced response time when offloading tasks in the IoV. The proposed method effectively transfers workloads to the fog computing layer while considering the constrained resources of car nodes. After choosing a suitable processing unit, the algorithm sends the job and its associated resources to the fog layer. The dataset is related to crisp values for fog computing for system utilization, latency, and task deadline time for over 5000 values. The task execution, latency, deadline of task, storage, CPU, and bandwidth utilizations are used for fuzzy set values. We proved the effectiveness of our proposed task scheduling framework via simulation tests, outperforming current algorithms in terms of task ratio by 13%, decreasing average turnaround time by 9%, minimizing makespan time by 15%, and effectively overcoming average latency time within the network parameters. The proposed technique shows better results and responses than previous techniques by scheduling the tasks toward fog layers with less response time and minimizing the overall time from task submission to completion.

ANN-Based Intelligent Secure Routing Protocol in Vehicular Ad Hoc Networks (VANETs) Using Enhanced AODV.

A vehicular ad hoc network (VANET) is a sophisticated wireless communication infrastructure incorporating centralized and decentralized control mechanisms, orchestrating seamless data exchange among vehicles. This intricate communication system relies on the advanced capabilities of 5G connectivity, employing specialized topological arrangements to enhance data packet transmission. These vehicles communicate amongst themselves and establish connections with roadside units (RSUs). In the dynamic landscape of vehicular communication, disruptions, especially in scenarios involving high-speed vehicles, pose challenges. A notable concern is the emergence of black hole attacks, where a vehicle acts maliciously, obstructing the forwarding of data packets to subsequent vehicles, thereby compromising the secure dissemination of content within the VANET. We present an intelligent cluster-based routing protocol to mitigate these challenges in VANET routing. The system operates through two pivotal phases: first, utilizing an artificial neural network (ANN) model to detect malicious nodes, and second, establishing clusters via enhanced clustering algorithms with appointed cluster heads (CH) for each cluster. Subsequently, an optimal path for data transmission is predicted, aiming to minimize packet transmission delays. Our approach integrates a modified ad hoc on-demand distance vector (AODV) protocol for on-demand route discovery and optimal path selection, enhancing request and reply (RREQ and RREP) protocols. Evaluation of routing performance involves the BHT dataset, leveraging the ANN classifier to compute accuracy, precision, recall, F1 score, and loss. The NS-2.33 simulator facilitates the assessment of end-to-end delay, network throughput, and hop count during the path prediction phase. Remarkably, our methodology achieves 98.97% accuracy in detecting black hole attacks through the ANN classification model, outperforming existing techniques across various network routing parameters.

Increasing rates of cesarean birth in Bangladesh: A household-level pooled analysis.

BACKGROUND: Cesarean birth (CB) rates have been increasing rapidly globally, including in Bangladesh. This study aimed to assess national trends in CB rates and to investigate associated factors in Bangladesh. METHODS: We analyzed data from the five most recent Bangladesh Demographic and Health Surveys (BDHS) between 2003 and 2018. A total of 27,328 ever-married women aged 15-49 who had a live birth in the 2 years preceding the survey were included in this study. We estimated the prevalence of CB from 2003 to 2018, as well as changes in the prevalence. Logistic regression analysis was used to measure the association between dependent and independent variables. RESULTS: The overall prevalence of CB among Bangladeshi mothers was 3.99% in 2003-04; this rate increased to 33.22% in 2017-18. The annual percentage change in CB rate was 16.34% from 2004 to 2017-18, which is alarming relative to the World Health Organization's cesarean birth recommended threshold. Several factors, such as maternal age, maternal and paternal education, working status of the mother, maternal BMI, age at first pregnancy, antenatal care (ANC) use, administrative division, and wealth status, had a significant influence on the rising rate of CB in Bangladesh. CONCLUSIONS: This study documents the alarming rate of CB increase in Bangladesh since 2003. It is critical that authorities implement more effective national monitoring measures to identify the causes of this dramatic increase and work to mitigate the rate of unnecessary CB in Bangladesh.

A La2O3/MXene composite electrode for supercapacitors with improved capacitance and cycling performance.

Developing efficient electrode materials is a key towards high power electrochemical energy storage devices. Two-dimensional (2D) MXene shows excellent conductivity and electrochemical performance among other materials. However, the restacking of MXene layers may degrade their specific capacity and cycling performance. Considering this challenge, here we have designed a composite made of 2D MXene nanosheets and lanthanum oxide (La2O3) nanoparticles to overcome the limitations. The bifunctionality of La2O3 nanoparticles prevents the restacking of MXene layers and enhances the electrochemical properties of the electrode due to its good Faradic characteristics. The specific capacitance of the La2O3/MXene composite electrode is 366 F/g at 1 A/g, which is 4.5 and 3 times higher than those of the individual La2O3 and MXene. The composite electrode displays a capacitance retention of 96% after 1,000 cycles, which is due to synergistic effects between the two components and indicates the potential of La2O3/MXene composite for supercapacitors.

A cohort study investigating the role of Bisphenol A in the molecular pathogenesis of breast cancer.

BACKGROUND: Breast cancer is an abnormal division of breast cells. Bisphenol A (BPA), an environmental toxicant, is identified as an emerging risk factor for breast cancer development. However, to the best of our knowledge, no previous study has investigated the BPA levels in breast cancer patients in Pakistan. The present study sought to explore the role of BPA in tumor growth among the Pakistani population. METHODS: The levels of BPA were analyzed in the serum samples of breast cancer patients and controls by using HPLC. To elucidate the role of BPA to initiate tumorigenic events in breast tissue different biochemical assays along with expression analysis of tumor markers were performed. RESULTS: The level of BPA in the serum samples of breast cancer patients was significantly higher than control. Histological analysis of breast cancer tissue samples revealed distinct subtypes of tumor, such as ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). There was a significant increase in ROS level while a significant decrease in the levels of superoxide dismutase (SOD) and catalase (CAT) enzymes in malignant breast tissue samples as compared to control tissue samples. We found upregulated expression of p53, ZEB1 and WNT1 genes at mRNA level in malignant breast tissue samples by 17 folds, 328 folds and 35 folds, respectively. p53 protein expression in malignant breast tissue samples was also enhanced at the translational level. CONCLUSION: Current findings suggest a relationship between BPA and the progression of breast cancer among the Pakistani population.

Enhancement of shelf-life of food items via immobilized enzyme nanoparticles on varied supports. A sustainable approach towards food safety and sustainability.

This study was designed to extend the shelf life of fruits and vegetables through a novel technique based on utilization of microbially driven enzyme glucose oxidase and casting a fine layer of hydrogen peroxide on the food item that protected the fruit from decay. The produced nanoparticles (ZnO, Ag) were ligated with Glucose Oxidize (GOx) purified from Aspergillus niger. Post ligation studies revealed that ligated enzymes display relatively enhanced activity. Four types of sprays were prepared in order to compare their effectiveness. Glucose oxidase/silver nanoparticles (GOx/AgNPs), glucose oxidase/zinc oxide nanoparticles (GOx/ZnONPs), AgNPs and ZnONPs sprays were applied to guava fruit samples as post-harvest therapeutic agents for a period of 15 days. Fruit quality parameters such as total suspended solids (TSS), pH, weight loss, DPPH free radical capturing performance and firmness confirms that usage of the bioconjugates especially that of GOx/ZnONP was curiously active to maintain the physical appearance of fruit well along with no such deterioration in chemical composition of fruit. Consequently, enzymes ligated on the surface of nanoparticles (ZnONP) are exceptional for extension of post-harvest shelf life of fruits such as guava.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis.

BACKGROUND: The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. METHODS: We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. RESULTS: There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. CONCLUSION: Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Pooling samples to increase testing capacity with Xpert Xpress SARS-CoV-2 during the Covid-19 pandemic in Lao People's Democratic Republic.

The COVID-19 pandemic created the need for large-scale testing of populations. However, most laboratories do not have sufficient testing capacity for mass screening. We evaluated pooled testing of samples, as a strategy to increase testing capacity in Lao PDR. Samples of consecutive patients were tested in pools of four using the Xpert Xpress SARS CoV-2 assay. Positive pools were confirmed by individual testing, and we describe the performance of the test and savings achieved. We also diluted selected positive samples to describe its effect on the assays CT values. 1,568 patients were tested in 392 pools of four. 361 (92.1%) pools were negative and 31 (7.9%) positive. 29/31 (93.5% (95%CI 77-99%) positive pools were confirmed by individual testing of the samples but, in 2/31 (6.5%) the four individual samples were negative, suggesting contamination. Pools with only one positive sample had higher CT values (lower RNA concentrations) than the respective individual samples, indicating a dilution effect, which suggested an increased risk of false negative results with dilutions >1:10. However, this risk may be low if the prevalence of infection is high, when pools are more likely to contain more than one positive sample. Pooling saved 67% of cartridges and substantially increased testing capacity. Pooling samples increased SARS-CoV-2 testing capacity and resulted in considerable cartridge savings. Given the need for high-volume testing, countries may consider implementation of pooling for SARS-CoV-2 screening.

Factors affecting the healthcare utilization from Shasthyo Suroksha Karmasuchi scheme among the below-poverty-line population in one subdistrict in Bangladesh: a cross sectional study.

BACKGROUND: Financing healthcare through out-of-pocket (OOP) payment is a major barrier in accessing healthcare for the poor people. The Health Economics Unit (HEU) of the Ministry of Health and Family Welfare of the government of Bangladesh has developed Shasthyo Suroksha Karmasuchi (SSK), a health protection scheme, with the aim of reducing OOP expenditure and improving access of the below-poverty-line (BPL) population to healthcare. The scheme started piloting in 2016 at Kalihati sub-district of Tangail District. Our objective was to assess healthcare utilization by the enrolled BPL population and to identify the factors those influencing their utilization of the scheme. METHOD: A cross-sectional household survey was conducted from July to September 2018 in the piloting sub-district. A total of 806 households were surveyed using a semi-structured questionnaire. Information on illness and sources of healthcare service were captured for the last 90 days before the survey. Multiple logistic regression models were applied to determine the factors related to utilization of healthcare from the SSK scheme and other medically trained providers (MTPs) by the SSK members for both inpatient and outpatient care. RESULT: A total of 781 (24.6%) people reported of suffering from illness of which 639 (81.8%) sought healthcare from any sources. About 8.0% (51 out of 639) of them sought healthcare from SSK scheme and 28.2% from other MTPs within 90 days preceding the survey. Households with knowledge about SSK scheme were more likely to utilize healthcare from the scheme and less likely to utilize healthcare from other MTPs. Non-BPL status and suffering from an accident/injury were significantly positively associated with utilization of healthcare from SSK scheme. CONCLUSION: Among the BPL population, healthcare utilization from the SSK scheme was very low compared to that of other MTPs. Effective strategies should be in place for improving knowledge of BPL population on SSK scheme and the benefits package of the scheme should be updated as per the need of the target population. Such initiative can be instrumental in increasing utilization of the scheme and ultimately will reduce the barriers of OOP payment among BPL population for accessing healthcare.

Factors Influencing the Efficiency of Public Hospitals in Saudi Arabia: A Qualitative Study Exploring Stakeholders' Perspectives and Suggestions for Improvement.

Objective: Despite an extensive literature on efficiency, qualitative evidence on the drivers of hospital efficiency is scant. This study examined the factors that influence the efficiencies of health service provision in public hospitals in the Kingdom of Saudi Arabia (KSA) and their potential remedies. Design: We employed a qualitative design involving semi-structured interviews conducted between July and September 2019. Participants were purposively selected and included policymakers and hospital managers drawn from districts, regional and national levels. Data were analyzed in Nvivo 12 based on a thematic approach. Setting: Key informants of Ministry of health in the KSA. Results: Respondents identified a range of different factors across the community, facility and the wider health system that influence inefficiencies in public hospitals in KSA. Ineffective hospital management, lack of strategic planning and goals, weak administrative leadership, and absence of monitoring hospital performance was noted to have a profound impact on hospital efficiency. The conditions of healthcare staff in respect to both skills, authority and psychological factors were considered to influence the efficiency level. Further, lack of appropriate data for decision making due to the absence of an appropriate health informatics system was regarded as a factor of inefficiency. At the community level, respondents described inadequate information on the healthcare needs and expectations of patients and the wider community as significant barriers to the provision of efficient services. To improve hospital efficiencies, respondents recommended that service delivery decisions are informed by data on community health needs; capacity strengthening and effective supervision of hospital staff; and judicious resource allocation. Conclusion: The study demonstrates that inefficiencies in health services remain a critical challenge in public hospitals in KSA. Extensive awareness-raising and training on efficient resource utilization among key health systems stakeholders are imperative to improving hospital performance. More research is needed to strengthen knowledge on hospital efficiency in light of the limited data on the topic in KSA and the wider Gulf region.

Household Microenvironment and Under-Fives Health Outcomes in Uganda: Focusing on Multidimensional Energy Poverty and Women Empowerment Indices.

Young children in low- and middle-income countries (LMICs) are vulnerable to adverse effects of household microenvironments. The UN Sustainable Development Goals (SDGs)-specifically SDG 3 through 7-urge for a comprehensive multi-sector approach to achieve the 2030 goals. This study addresses gaps in understanding the health effects of household microenvironments in resource-poor settings. It studies associations of household microenvironment variables with episodes of acute respiratory infection (ARI) and diarrhoea as well as with stunting among under-fives using logistic regression. Comprehensive data from a nationally representative, cross-sectional demographic and health survey (DHS) in Uganda were analysed. We constructed and applied the multidimensional energy poverty index (MEPI) and the three-dimensional women empowerment index in multi-variate regressions. The multidimensional energy poverty was associated with higher risk of ARI (OR = 1.32, 95% CI 1.10 to 1.58). Social independence of women was associated with lower risk of ARI (OR= 0.91, 95% CI 0.84 to 0.98), diarrhoea (OR = 0.93, 95% CI 0.88 to 0.99), and stunting (OR = 0.83, 95% CI 0.75 to 0.92). Women's attitude against domestic violence was also significantly associated with episodes of ARI (OR = 0.88, 95% CI 0.82 to 0.93) and diarrhoea (OR = 0.89, 95% CI 0.84 to 0.93) in children. Access to sanitation facilities was associated with lower risk of ARI (OR = 0.55, 95% CI 0.45 to 0.68), diarrhoea (OR = 0.83, 95% CI 0.71 to 0.96), and stunting (OR = 0.64, 95% CI 0.49 to 0.86). Investments targeting synergies in integrated energy and water, sanitation and hygiene, and women empowerment programmes are likely to contribute to the reduction of the burden from early childhood illnesses. Research and development actions in LMICs should address and include multi-sector synergies.

Multi-trait genomic prediction using in-season physiological parameters increases prediction accuracy of complex traits in US wheat.

BACKGROUND: Recently genomic selection (GS) has emerged as an important tool for plant breeders to select superior genotypes. Multi-trait (MT) prediction model provides an opportunity to improve the predictive ability of expensive and labor-intensive traits. In this study, we assessed the potential use of a MT genomic prediction model by incorporating two physiological traits (canopy temperature, CT and normalized difference vegetation index, NDVI) to predict 5 complex primary traits (harvest index, HI; grain yield, GY; grain number, GN; spike partitioning index, SPI; fruiting efiiciency, FE) using two cross-validation schemes CV1 and CV2. RESULTS: In this study, we evaluated 236 wheat genotypes in two locations in 2 years. The wheat genotypes were genotyped with genotyping by sequencing approach which generated 27,466 SNPs. MT-CV2 (multi-trait cross validation 2) model improved predictive ability by 4.8 to 138.5% compared to ST-CV1(single-trait cross validation 1). However, the predictive ability of MT-CV1 was not significantly different compared to the ST-CV1 model. CONCLUSIONS: The study showed that the genomic prediction of complex traits such as HI, GN, and GY can be improved when correlated secondary traits (cheaper and easier phenotyping) are used. MT genomic selection could accelerate breeding cycles and improve genetic gain for complex traits in wheat and other crops.

Expression of HK2, PKM2, and PFKM Is Associated with Metastasis and Late Disease Onset in Breast Cancer Patients.

The reprogramming of energy metabolism is one of the hallmarks of cancer and is crucial for tumor progression. Altered aerobic glycolysis is a well-known characteristic of cancer cell metabolism. In the present study, the expression profiles of key metabolic genes (HK2, PFKM, and PKM2) were assessed in the breast cancer cohort of Pakistan using quantitative polymerase chain reaction (qPCR) and IHC. Expression patterns were correlated with molecular subtypes and clinical parameters in the patients. A significant upregulation of key glycolytic genes was observed in tumor samples in comparison to their adjacent controls (p < 0.0001). The expression of the studied glycolytic genes was significantly increased in late clinical stages, positive nodal involvement, and distant metastasis (p < 0.05). HK2 and PKM2 were found to be upregulated in luminal B, whereas PFKM was overexpressed in the luminal A subtype of breast cancer. The genes were positively correlated with the proliferation marker Ki67 (p < 0.001). Moreover, moderate positive linear correlations between HK2 and PKM2 (r = 0.476), HK2 and PFKM (r = 0.473), and PKM2 and PFKM (r = 0.501) were also observed (p < 0.01). These findings validate that the key regulatory genes in glycolysis can serve as potential biomarkers and/or molecular targets for breast cancer management. However, the clinical significance of these molecules needs to be further validated through in vitro and in vivo experiments.

Household food insecurity, maternal nutrition, environmental risks and infants' health outcomes: protocol of the IMPALA birth cohort study in Uganda.

INTRODUCTION: In low- and middle-income countries (LMICs), food insecurity and undernutrition disproportionately affect women of reproductive age, infants and young children. The disease burden from undernutrition in these vulnerable sections of societies remains a major concern in LMICs. Biomass fuel use for cooking is also common in LMICs. Empirical evidence from high-income countries indicates that early life nutritional and environmental exposures and their effect on infant lung function are important; however, data from sub-Saharan Africa are scarce. AIM: To estimate the association between infant lung function and household food insecurity, energy poverty and maternal dietary diversity. METHODS AND ANALYSIS: Pregnant women will be recruited in an existing Health and Demographic Surveillance Site in South-West Uganda. Household food insecurity, sources and uses of energy, economic measures and maternal dietary diversity will be collected during pregnancy and after birth. Primary health outcomes will be infant lung function determined by tidal breath flow and volume analysis at 6-10 weeks of age. Infant weight and length will also be collected.A household Food Consumption Score and Minimum Dietary Diversity for Women (MDD-W) indicator will be constructed. The involved cost of dietary diversity will be estimated based on MDD-W. The association between household level and mothers' food access indicators and infant lung function will be evaluated using regression models. The Multidimensional Energy Poverty Index (MEPI) will be estimated and used as an indicator of households' environmental exposures. The association between household MEPI and infant lung function will be assessed using econometric models. ETHICS AND DISSEMINATION: Ethical approvals have been obtained from Liverpool School of Tropical Medicine (18-059), the Uganda Virus Research Institute Ethics Committee (097/2018) and Uganda National Council for Science and Technology (SS 4846). Study results will be shared with participants, policy-makers, other stakeholders and published in peer-reviewed journals.