Nations Development Programme Research Articles

Залучення іноземних інвестицій для повоєнної відбудови: досвід країн Західних Балкан

The article is dedicated to summarizing and comparing the experience of attracting foreign direct investment (FDI) for post-war reconstruction in the Western Balkans and its significance for Ukraine amid ongoing military aggression and the need for post-war rebuilding. It characterizes the experiences of Croatia, Serbia, Bosnia and Herzegovina, Albania, Montenegro, North Macedonia, and Kosovo, which suffered destruction during the Yugoslav wars in the Balkans and used FDI as a key tool for economic recovery. The paper examines legislative, tax, institutional, and infrastructural measures aimed at attracting foreign capital, including the establishment of free economic zones, support for small and medium-sized enterprises, tax reductions, and subsidies. The importance of legal protection, political stability, and anti-corruption measures for creating a favorable investment environment is argued. Additionally, the article highlights the critical role of international organizations such as the World Bank, the European Bank for Reconstruction and Development (EBRD), the European Investment Bank (EIB), and the United Nations Development Programme (UNDP), which provided funding for infrastructure projects and institutional reform. Their involvement contributed to the reconstruction of key economic sectors and prepared the countries for European integration. The Balkan experience is valuable for Ukraine, as the current challenges and reconstruction needs after the war share similar features. Ukraine can leverage the tools and approaches of the Western Balkan countries to develop its strategy for attracting FDI, including European integration processes, legal system improvements, anti-corruption reforms, and the stimulation of domestic investment.

Impact of national development programs and legislations on the cereal crops seed sector in Iraq

Agriculture is a crucial economic sector in Iraq, benefiting from abundant natural resources, skilled labor and essential infrastructure. These elements have enabled the sector to play a significant role in agricultural development, particularly in the production of strategic crops. Between 2010 and 2020, the Iraqi government implemented various policies and legislation aimed at advancing the seed sector. These efforts focused on supporting and developing seed-producing entities across governmental, mixed and private sectors, positioning them as essential instruments for executing the strategies of the government. Modern agricultural technologies, especially improved seeds, have been vital in boosting productivity and reducing costs. Therefore, the government has prioritized the adoption of advanced technologies within its agricultural policies and programs. These scientific innovations, particularly in seed production, are key to enhancing the cultivation of strategic crops. Improved seeds have thus become a cornerstone of Iraq’s agricultural development, contributing to both increased productivity and sustainable farming practices. This research aims to clarify the role of national development programs and legislation in strengthening the seed sector and increasing the production of strategic crops in Iraq. It reviews the progress in grain crop production between 2006 and 2020 and examines the most significant aspects of government policies, highlighting how legislation and national programs have played a pivotal role in the production of higher-grade seeds and the development of strategic crop cultivation.

The Role of TVET Colleges in Addressing the Needs of NEET Youth in a South African Province

ABSTRACT This study is justified by the ever-rising poverty, unemployment, and inequality that South African youth experience, particularly not in education or employment and training (NEET) youth. It explored and evaluated the functions of Technical Vocational Education and Training (TVET) in the National Development Plan (NDP) with a focus on the requirements of NEET youth in a province of South Africa using theories of human capital and empowerment. The methods and mitigating measures that TVET are implementing to address the needs of NEET youths were captured using a phenomenological and explorative research technique to achieve this purpose. Convenience and purposive sampling were used to choose participants for the semi-structured interviews with TVET managers (N = 2) and focus groups for educators (N = 20). Following thematic data analysis, these four themes were identified: (i) Unlocking Youth Potential through TVET, (ii) Relationship between TVET curriculum and economic development, (iii) TVET’s Contribution to National Development and Youth Empowerment, (iv) Constraints faced by the youth in implementing the national development plan. The themes illustrated the government’s obligation to eradicate youth inactivity by providing them with a variety of skills through TVET frameworks. Young people are therefore advised to actively participate in TVET initiatives designed to end poverty and youth unemployment. Additionally, it is recommended that the South African government, TVET colleges, and industry work together to ensure that national development programs, particularly those that focus on the economic empowerment and development of youths, may be accomplished to attain the NDP 2030 target on schedule.

Associations of long-term nitrogen dioxide exposure with a wide spectrum of diseases: a prospective cohort study of 0·5 million Chinese adults

Little evidence is available on the long-term health effects of nitrogen dioxide (NO2) in low-income and middle-income populations. We investigated the associations of long-term NO2 exposure with the incidence of a wide spectrum of disease outcomes, based on data from the China Kadoorie Biobank. This prospective cohort study involved 512 724 Chinese adults aged 30-79 years recruited from ten areas of China during 2004-08. Time-varying Cox regression models yielded adjusted hazard ratios (HRs) for the associations of long-term NO2 exposure with aggregated disease incidence endpoints classified by 14 ICD-10 chapters, and incidences of 12 specific diseases selected from three key ICD-10 chapters (cardiovascular, respiratory, and musculoskeletal diseases) found to be robustly associated with NO2 in the analyses of aggregated endpoints. All models were stratified by age-at-risk (in 1-year scale), study area, and sex, and were adjusted for education, household income, smoking status, alcohol intake, cooking fuel type, heating fuel type, self-reported health status, BMI, physical activity level, temperature, and relative humidity. The analysis of 512 709 participants (mean baseline age 52·0 years [SD 10·7]; 59·0% female and 41·0% male) included approximately 6·5 million person-years of follow-up. Between 5285 and 144 852 incident events were recorded for each of the 14 aggregated endpoints. Each 10 μg/m3 higher annual average NO2 exposure was associated with higher risks of chapter-specific endpoints, especially cardiovascular (n=144 852; HR 1·04 [95% CI 1·02-1·05]), respiratory (n=73 232; 1·03 [1·01-1·05]), musculoskeletal (n=54 409; 1·11 [1·09-1·14]), and mental and behavioural (n=5361; 1·12 [1·05-1·21]) disorders. Further in-depth analyses on specific diseases found significant positive supra-linear associations with hypertensive disease (1·08 [1·05-1·11]), lower respiratory tract infection (1·03 [1·01-1·06]), arthrosis (1·15 [1·09-1·21]), intervertebral disc disorders (1·13 [1·09-1·17]), and spondylopathies (1·05 [1·01-1·10]), and linear associations with ischaemic heart disease (1·03 [1·00-1·05]), ischaemic stroke (1·08 [1·06-1·11]), and asthma (1·15 [1·04-1·27]), whereas intracerebral haemorrhage (1·00 [0·95-1·06]), other cerebrovascular disease (0·98 [0·96-1·01]), acute upper respiratory infection (1·03 [0·96-1·09]), and chronic lower respiratory disease (0·98 [0·95-1·02]) showed no significant association. NO2 exposure showed robust null association with external causes (n=32 907; 0·98 [0·95-1·02]) as a negative control. In China, long-term NO2 exposure was associated with a range of diseases, particularly cardiovascular, respiratory, and musculoskeletal diseases. These associations underscore the pressing need to implement the recently tightened WHO air quality guidelines. Wellcome Trust, UK Medical Research Council, Cancer Research UK, British Heart Foundation, National Natural Science Foundation of China, National Key Research and Development Program of China, Sino-British Fellowship Trust, and Kadoorie Charitable Foundation.

Deep learning using histological images for gene mutation prediction in lung cancer: a multicentre retrospective study.

Accurate detection of driver gene mutations is crucial for treatment planning and predicting prognosis for patients with lung cancer. Conventional genomic testing requires high-quality tissue samples and is time-consuming and resource-consuming, and as a result, is not available for most patients, especially those in low-resource settings. We aimed to develop an annotation-free Deep learning-enabled artificial intelligence method to predict GEne Mutations (DeepGEM) from routinely acquired histological slides. In this multicentre retrospective study, we collected data for patients with lung cancer who had a biopsy and multigene next-generation sequencing done at 16 hospitals in China (with no restrictions on age, sex, or histology type), to form a large multicentre dataset comprising paired pathological image and multiple gene mutation information. We also included patients from The Cancer Genome Atlas (TCGA) publicly available dataset. Our developed model is an instance-level and bag-level co-supervised multiple instance learning method with label disambiguation design. We trained and initially tested the DeepGEM model on the internal dataset (patients from the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China), and further evaluated it on the external dataset (patients from the remaining 15 centres) and the public TCGA dataset. Additionally, a dataset of patients from the same medical centre as the internal dataset, but without overlap, was used to evaluate the model's generalisation ability to biopsy samples from lymph node metastases. The primary objective was the performance of the DeepGEM model in predicting gene mutations (area under the curve [AUC] and accuracy) in the four prespecified groups (ie, the hold-out internal test set, multicentre external test set, TCGA set, and lymph node metastases set). Assessable pathological images and multigene testing information were available for 3697 patients who had biopsy and multigene next-generation sequencing done between Jan 1, 2018, and March 31, 2022, at the 16 centres. We excluded 60 patients with low-quality images. We included 3767 images from 3637 consecutive patients (1978 [54·4%] men, 1514 [41·6%] women, 145 [4·0%] unknown; median age 60 years [IQR 52-67]), with 1716 patients in the internal dataset, 1718 patients in the external dataset, and 203 patients in the lymph node metastases dataset. The DeepGEM model showed robust performance in the internal dataset: for excisional biopsy samples, AUC values for gene mutation prediction ranged from 0·90 (95% CI 0·77-1·00) to 0·97 (0·93-1·00) and accuracy values ranged from 0·91 (0·85-0·98) to 0·97 (0·93-1·00); for aspiration biopsy samples, AUC values ranged from 0·85 (0·80-0·91) to 0·95 (0·86-1·00) and accuracy values ranged from 0·79 (0·74-0·85) to 0·99 (0·98-1·00). In the multicentre external dataset, for excisional biopsy samples, AUC values ranged from 0·80 (95% CI 0·75-0·85) to 0·91 (0·88-1·00) and accuracy values ranged from 0·79 (0·76-0·82) to 0·95 (0·93-0·96); for aspiration biopsy samples, AUC values ranged from 0·76 (0·70-0·83) to 0·87 (0·80-0·94) and accuracy values ranged from 0·76 (0·74-0·79) to 0·97 (0·96-0·98). The model also showed strong performance on the TCGA dataset (473 patients; 535 slides; AUC values ranged from 0·82 [95% CI 0·71-0·93] to 0·96 [0·91-1·00], accuracy values ranged from 0·79 [0·70-0·88] to 0·95 [0·90-1·00]). The DeepGEM model, trained on primary region biopsy samples, could be generalised to biopsy samples from lymph node metastases, with AUC values of 0·91 (95% CI 0·88-0·94) for EGFR and 0·88 (0·82-0·93) for KRAS and accuracy values of 0·85 (0·80-0·88) for EGFR and 0·95 (0·92-0·96) for KRAS and showed potential for prognostic prediction of targeted therapy. The model generated spatial gene mutation maps, indicating gene mutation spatial distribution. We developed an AI-based method that can provide an accurate, timely, and economical prediction of gene mutation and mutation spatial distribution. The method showed substantial potential as an assistive tool for guiding the clinical treatment of patients with lung cancer. National Natural Science Foundation of China, the Science and Technology Planning Project of Guangzhou, and the National Key Research and Development Program of China. For the Chinese translation of the abstract see Supplementary Materials section.

Safety and efficacy of early versus delayed acetylsalicylic acid after surgery for spontaneous intracerebral haemorrhage in China (E-start): a prospective, multicentre, open-label, blinded-endpoint, randomised trial

Patients with non-traumatic intracerebral haemorrhage have a substantial risk of major adverse cardiovascular and cerebrovascular events, including ischaemic stroke, after surgery. The optimal timing of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage in patients at high risk of postoperative ischaemic events has not been characterised. We aimed to investigate the safety and efficacy of early versus late initiation of antiplatelet therapy after surgery for spontaneous intracerebral haemorrhage. This prospective, open-label, blinded-endpoint, randomised trial was done at eight stroke centres in China. Eligible patients were aged 18-70 years, undergoing surgery for the evacuation of spontaneous intracerebral haemorrhage, and had a high risk of postoperative ischaemic events. Using the minimisation method in an online randomisation system, patients were randomly assigned (1:1) to receive 100 mg acetylsalicylic acid once per day in either the early-start group (starting on the third day after surgery until the 90th day after surgery) or the late-start group (starting on the 30th day after surgery until the 90th day after surgery). Medication was taken orally or delivered via a feeding tube. The primary efficacy outcome was a composite of new major ischaemic cardiovascular, cerebrovascular, or peripheral vascular events within 90 days and the primary safety outcome was any intracranial bleeding within 90 days, both measured in the intention-to-treat population. The trial is registered at ClinicalTrials.gov, NCT04820972, and is complete. From May 1, 2021, to May 1, 2023, 7323 patients were screened, of whom 269 (4%) were enrolled and randomly assigned: 134 to the early-start group and 135 to the late-start group. 195 (72%) patients were male, 74 (28%) were female, and the median age was 60·2 years (IQR 52·0-66·5). Haematomas were supratentorial and deep in most (170 [63%] of 269) patients. Ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events occurred within 90 days after surgery in 27 (20%) of 134 patients in the early-start group and 42 (31%) of 135 patients in the late-start group (odds ratio 0·56 [95% CI 0·32-0·98]; p=0·041). Intracranial bleeding occurred in one (1%) of 134 patients in the early-start group and four (3%) of 135 patients in the late-start group. Non-bleeding serious adverse events occurred in 57 (42%) of 134 patients in the early-start group and 57 (42%) of 135 patients in the late-start group. Starting acetylsalicylic acid on the third day after surgery for spontaneous intracerebral haemorrhage in Chinese patients at high risk of postoperative ischaemic events resulted in fewer postoperative ischaemic major cardiovascular, cerebrovascular, or peripheral vascular events than starting acetylsalicylic acid therapy at 30 days, with no increased risk of intracranial bleeding. Whether early initiation of acetylsalicylic acid therapy is safe and improves clinical outcomes for broader populations of patients with spontaneous intracerebral haemorrhage requires further research. The National Key Research and Development Program of China.

Anwar Fazal-A Breastfeeding Advocate Extraordinaire.

Anwar Fazal has been a driving force in the founding of several civil society organizations in the areas of health, human rights, environment, and peace, that have been at the forefront of activism locally, nationally, and globally. In this interview, he shares his journey of 6 decades, involving a multiverse of public interest issues, which led him into the breastfeeding movement. It began with the setting up of the International Baby Food Action Network (IBFAN), a pioneering action that triggered the formation of Health Action International (HAI), Pesticide Action Network (PAN), and the World Alliance for Breastfeeding Action (WABA). Each of these resulted in several unique frameworks and codes relating to the marketing of infant foods, pharmaceuticals, and pesticides. They also led to the formation of World Breastfeeding Week, now being celebrated globally. Anwar studied Economics at the University of Malaya and did his postgraduate studies in Education. Anwar has served as a visiting professor at the University of Science Malaysia and the International Islamic University Malaysia (IIUM). He is the recipient of the Right Livelihood Award, popularly known as the "Alternative Nobel Prize," for his work on breastfeeding and infant nutrition and other health, environmental, and consumer issues. La Leche League International (LLLI) and the United Nations Development Programme (UNDP) have honored him with the International Health Award and the Millennium Development Goals Award. He has written extensively on breastfeeding. He is currently Chairperson Emeritus of the World Alliance for Breastfeeding Action (WABA) and continues to speak out actively on protecting, promoting, and supporting breastfeeding.

Gender and sustainability at the heart of the Amazon: a look at the bioentrepreneurs

The popular and solidarity economy (PSE) aims to achieve collective well-being through activities based on solidarity. The Amazon region of the Republic of Ecuador is closely linked to extractive activities, which risk affecting the health of local populations and accelerating forest degradation. Furthermore, poverty in this region affects 57% of the population, forcing families to engage in harmful forestry activities with significant environmental consequences. International cooperation, providing financing to promote bioenterprises, has generated sustainable alternatives for these populations. In this context, associativity emerges as a mechanism that generates sources of income for families dedicated to the preservation of forests, presenting itself as a viable solution to this problem. This research aims to determine how the financing of international cooperation influences the associative processes of the PSE, taking as a case study the Association of Wayusa Producers of Limoncocha, Ecuador. This association is part of the " Proamazonía " project financed by the Ecuadorian government and the United Nations Development Program (UNDP). Data was collected through semi-structured surveys and focus groups with key stakeholders. The results suggest that it is possible to achieve both economic and social benefits through the associative process. These include empowering Indigenous women, integrating them into the production process under fair conditions and preserving local culture. Consequently, this improves the quality of life of families and, at the same time, prevents the expansion of the agricultural frontier, promoting the economic and environmental sustainability of the area.

Intensive Blood-Pressure Control in Patients with Type 2 Diabetes.

Effective targets for systolic blood-pressure control in patients with type 2 diabetes are unclear. We enrolled patients 50 years of age or older with type 2 diabetes, elevated systolic blood pressure, and an increased risk of cardiovascular disease at 145 clinical sites across China. Patients were randomly assigned to receive intensive treatment that targeted a systolic blood pressure of less than 120 mm Hg or standard treatment that targeted a systolic blood pressure of less than 140 mm Hg for up to 5 years. The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes. Multiple imputation was used for missing outcome data, with an assumption that the data were missing at random. Of 12,821 patients (6414 patients in the intensive-treatment group and 6407 in the standard-treatment group) enrolled from February 2019 through December 2021, 5803 (45.3%) were women; the mean (±SD) age of the patients was 63.8±7.5 years. At 1 year of follow-up, the mean systolic blood pressure was 121.6 mm Hg (median, 118.3 mm Hg) in the intensive-treatment group and 133.2 mm Hg (median, 135.0 mm Hg) in the standard-treatment group. During a median follow-up of 4.2 years, primary-outcome events occurred in 393 patients (1.65 events per 100 person-years) in the intensive-treatment group and 492 patients (2.09 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P<0.001). The incidence of serious adverse events was similar in the treatment groups. However, symptomatic hypotension and hyperkalemia occurred more frequently in the intensive-treatment group than in the standard-treatment group. Among patients with type 2 diabetes, the incidence of major cardiovascular events was significantly lower with intensive treatment targeting a systolic blood pressure of less than 120 mm Hg than with standard treatment targeting a systolic blood pressure of less than 140 mm Hg. (Funded by the National Key Research and Development Program of the Ministry of Science and Technology of China and others; BPROAD ClinicalTrials.gov number, NCT03808311.).

The Effects of Cognitive Self-Consciousness, Cultural Values, and Socioeconomic Context on Anxiety in Youth: A Meta-Analysis

Youth mental health is a global health priority due to its increasing prevalence and adverse outcomes. Although the relationship between metacognitions and anxiety is well-documented in adults, further research is needed for the younger populations. This research examines two questions: (a) What is the correlation between cognitive self-consciousness and anxiety in children and adolescents? (b) Is this correlation moderated by cultural and socioeconomic differences? Based on 22 effect sizes from 8,459 participants in 11 countries, a meta-analysis was performed to find the overall effect size, heterogeneity, publication bias, and the moderating effect of Hofstede’s four cultural dimensions and United Nation Development Programme’s (UNDP) Human Development Index (HDI). Using the random-effects model, the results revealed that cognitive self-consciousness ( r = .312, p &lt; .0001, 95% confidence interval: [.257, .365]) showing moderate effect size in association with anxiety in children and adolescents. Meta-regressions indicated that power distance, masculinity, and HDI were important moderators. The findings show a significant correlation between cognitive self-consciousness and mental wellness in youth. The results have important implications for understanding the influence of cultural beliefs and national-level context on the associations between cognition and psychopathology. This article provides consistent evidence that there is a lack of mental health research resources in the Global South.

Neoadjuvant and adjuvant toripalimab for locoregionally advanced nasopharyngeal carcinoma: a randomised, single-centre, double-blind, placebo-controlled, phase 2 trial

Patients with locoregionally advanced nasopharyngeal carcinoma with a high pretreatment plasma concentration of Epstein-Barr virus (EBV) DNA remain at high risk for recurrence after concurrent chemoradiotherapy. This study aimed to compare the efficacy and safety of neoadjuvant-adjuvant treatment with the PD-1 inhibitor toripalimab and concurrent chemoradiotherapy versus placebo and concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. This randomised, single-centre, double-blind, placebo-controlled, phase 2 trial was conducted at Sun Yat-sen University Cancer Centre in Guangzhou, China. Adult patients (aged 18-65 years) with newly diagnosed high-risk stage III-IVa locoregionally advanced nasopharyngeal carcinoma, with a pretreatment plasma EBV DNA concentration of at least 1500 copies per mL and an Eastern Cooperative Oncology Group performance score of 0-1, were eligible. Patients were randomly assigned (2:1) using an interactive web response system (block size of six), stratified by TNM stage (III vs IVa), to neoadjuvant toripalimab (240 mg intravenously) or placebo once every 2 weeks for two cycles, followed by concurrent cisplatin (100 mg/m2 intravenously) on days 1, 22, and 43 during intensity-modulated radiotherapy and adjuvant toripalimab (240 mg intravenously) or placebo once every 3 weeks for up to eight cycles. The primary endpoint was 2-year progression-free survival in the intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT03925090, and is closed to enrolment; follow-up is ongoing. Between Dec 6, 2019, and Dec 9, 2021, 150 patients were enrolled and randomly assigned to the toripalimab group (n=100) or placebo group (n=50). 115 (77%) patients were male and 35 (23%) were female. As of data cutoff (May 31, 2024), median follow-up for progression-free survival was 37·8 months (IQR 34·2-46·5) for the intention-to-treat population analyses. 2-year progression-free survival was higher in the toripalimab group (92·0% [95% CI 86·7-97·3]) than in the placebo group (74·0% [61·8-86·2]; stratified hazard ratio 0·40 [95% CI 0·18-0·89]; log-rank p=0·019). The most common grade 3 or worse acute adverse events (occurring within 1 year of randomisation) were leukopenia (40 [40%] of 99 patients in the toripalimab group vs 22 [44%] of 50 patients in the placebo group), mucositis (28 [28%] vs ten [20%]), neutropenia (17 [17%] vs nine [18%]), anaemia (16 [16%] vs five [10%]), and weight loss (12 [12%] vs six [12%]). The most common grade 3 or worse late adverse events (occurring >1 year after randomisation) was auditory or hearing loss (eight [8%] vs four [8%]). Immune-mediated adverse events of grade 3 or worse occurred in ten (10%) patients only in the toripalimab group. One (2%) of 50 patients in the placebo group died due to septic shock caused by bacteraemia considered not treatment related. There were no treatment-related deaths in the toripalimab group. Our findings suggested that a so-called sandwich approach involving toripalimab (in the neoadjuvant and adjuvant phases) combined with concurrent chemoradiotherapy could be a highly promising therapy for the treatment of locoregionally advanced nasopharyngeal carcinoma. Phase 3 non-inferiority trials are warranted comparing neoadjuvant and adjuvant toripalimab versus cisplatin plus gemcitabine neoadjuvant chemotherapy combined with concurrent chemoradiotherapy. National Key Research and Development Program of China, National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Science and Technology Program of Guangzhou, Sun Yat-sen University Clinical Research 5010 Program, Innovative Research Team of High-level Local Universities in Shanghai, Postdoctoral Innovative Talent Support Program, Planned Science and Technology Project of Guangdong Province, Key Youth Teacher Cultivating Program of Sun Yat-sen University, and Fundamental Research Funds for the Central Universities. For the Chinese translation of the abstract see Supplementary Materials section.

A series of patients infected with the emerging tick-borne Yezo virus in China: an active surveillance and genomic analysis

Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV. In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses. A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations. Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms. National Key Research and Development Program of China. For the Chinese translation of the abstract see Supplementary Materials section.

Population-based prevalence of self-reported pediatric diabetes and screening for undiagnosed type 2 diabetes in Chinese children in years 2017–2019, a cross-sectional study

The worldwide geographical and temporal variation in the prevalence of diabetes represents a challenge, but also an opportunity for gaining etiological insights. Encompassing the bulk of East Asians, a large and distinct proportion of the world population, China can be a source of valuable epidemiological insights for diabetes, especially in early life, when pathophysiology begins. We carried out a nationwide, epidemiological survey of Prevalence and Risk of Obesity and Diabetes in Youth (PRODY) in China, from 2017 to 2019, to estimate the population-based prevalence of diagnosed pediatric diabetes and screen for undiagnosed pediatric type 2 diabetes (T2D). PRODY was a nation-wide, school population-based, cross-sectional, multicenter survey by questionnaire, fasting urine glucose test and simple oral glucose tolerance test (s-OGTT), among a total number of 193,801 general-population children and adolescents (covered a pediatric population of more than 96.8 million), aged 3-18, from twelve provinces across China. The prevalence of the self-reported pediatric diabetes, the proportion of subtypes, the crude prevalence of undiagnosed T2D and prediabetes in general juvenile population and the main risk factors of type 1 (T1D) and type 2 (T2D) diabetes had been analyzed in the study. The prevalence of all self-reported pediatric diabetes was estimated at 0.62/1000 (95% CI: 0.51-0.74), with T1D at 0.44/1000 (95% CI: 0.35-0.54) and T2D at 0.18/1000 (95% CI: 0.13-0.25). For undiagnosed T2D, the crude prevalence was almost ten-fold higher, at 1.59/1000, with an estimated extra 28.45/1000 of undiagnosed impaired glucose tolerance (IGT) and 53.74/1000 of undiagnosed impaired fasting glucose (IFG) by s-OGTT screening. Maternal diabetes history is the major risk factors for all subtypes of pediatric diabetes in China. The PRODY study provides the first population-based estimate of the prevalence of pediatric diabetes China and reveals a magnitude of the problem of undiagnosed pediatric T2D. We propose a practical screening strategy by s-OGTT to address this serious gap. The National Key Research and Development Programme of China, Key R&D Program of Zhejiang, the National Natural Science Foundation of China and the Zhejiang Provincial Key Disciplines of Medicine, Key R&D Program Projects in Zhejiang Province.

Effect of heatwaves on mortality of Alzheimer's disease and other dementias among elderly aged 60 years and above in China, 2013–2020: a population-based study

BackgroundChina has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. MethodsThe study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013-2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. FindingsA total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1·140 (95% CI: 1·118, 1·163) under the mildest heatwave to 1·459 (95% CI: 1·403, 1·518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12·281% (95% CI: 10·555%, 14·015%) to 31·460% (95% CI: 28·724%, 34·124%). InterpretationThe study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. FundingThis work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

Pyrotinib and trastuzumab combination treatment synergistically overcomes HER2 dependency in HER2-positive breast cancer: insights from the PHILA trial

The PHILA study suggests that pyrotinib, trastuzumab, and docetaxel significantly improved progression-free survival (PFS) compared with placebo, trastuzumab, and docetaxel in patients with untreated HER2-positive metastatic breast cancer. In this study, we aimed to investigate the synergistic mechanisms of pyrotinib plus trastuzumab and provide further insights for the PHILA trial. The invitro activity of combination treatments was assessed through cell biological and biochemical experiments. The invivo efficacy was evaluated in cell-derived xenografts, a TUBO tumour model, and one clinical case. Next-generation sequencing was performed on circulating tumour DNA (ctDNA) from patients in the PHILA trial. The combination of pyrotinib and trastuzumab more effectively inhibited cell growth than pyrotinib or trastuzumab alone in models of HER2-dependent breast cancer. It potentiated membrane HER2 ubiquitination and downregulation, which resulted in a comprehensive blockade of the HER2 signalling pathway. The pyrotinib-altered membrane HER2 levels had no significant effect on trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC). We further validated the synergistic mechanisms in TUBO tumours and one clinical case, rather than models of HCC1954cells harbouring the PIK3CA H1047R mutation. Similarly, in our centre cohort of the PHILA study, patients with genetic alterations in the HER2 signalling cascade had significantly shorter median PFS than individuals with the wild-type pathway. Our findings underscore the robust synergy between pyrotinib and trastuzumab in overcoming HER2 dependency and provide a rationale for pyrotinib, trastuzumab, and docetaxel as one of the optimal choices for patients with untreated HER2-positive metastatic breast cancer, who are dependent on the HER2 signalling cascade. This work was supported by the National Key Research and Development Program of China (2021YFF1201300), the National Natural Science Foundation of China (82172875), the CAMS Innovation Fund for Medical Sciences (CIFMS) (2022-I2M-2-001), and the Joint Innovative Fund of Beijing Natural Science Foundation and Changping District (L234004).

Single cell atlas reveals multilayered metabolic heterogeneity across tumour types

Metabolic reprogramming plays a pivotal role in cancer progression, contributing to substantial intratumour heterogeneity and influencing tumour behaviour. However, a systematic characterization of metabolic heterogeneity across multiple cancer types at the single-cell level remains limited. We integrated 296 tumour and normal samples spanning six common cancer types to construct a single-cell compendium of metabolic gene expression profiles and identify cell type-specific metabolic properties and reprogramming patterns. A computational approach based on non-negative matrix factorization (NMF) was utilised to identify metabolic meta-programs (MMPs) showing intratumour heterogeneity. In-vitro cell experiments were conducted to confirm the associations between MMPs and chemotherapy resistance, as well as the function of key metabolic regulators. Survival analyses were performed to assess clinical relevance of cellular metabolic properties. Our analysis revealed shared glycolysis upregulation and divergent regulation of citric acid cycle across different cell types. In malignant cells, we identified a colorectal cancer-specific MMP associated with resistance to the cuproptosis inducer elesclomol, validated through in-vitro cell experiments. Furthermore, our findings enabled the stratification of patients into distinct prognostic subtypes based on metabolic properties of specific cell types, such as myeloid cells. This study presents a nuanced understanding of multilayered metabolic heterogeneity, offering valuable insights into potential personalized therapies targeting tumour metabolism. National Key Research and Development Program of China (2021YFA1300601). National Natural Science Foundation of China (key grants 82030081 and 81874235). The Shenzhen High-level Hospital Construction Fund and Shenzhen Basic Research Key Project (JCYJ20220818102811024). The Lam Chung Nin Foundation for Systems Biomedicine.

DEVELOPMENT OF A SYSTEMATIC APPROACH TO ASSESSING THE COMPLIANCE OF UNIVERSITY EDUCATIONAL PROGRAMS WITH THE UN SUSTAINABLE DEVELOPMENT GOALS

The purpose of the article is to develop and test in practice a systematic approach to assessing the compliance of educational programs of universities with the goals of sustainable development of the United Nations. The systematic approach includes the development of a sequence of development and approval of a questionnaire to determine the degree of compliance of educational programs of universities with the goals of sustainable development. Methodology. The survey was based on a comparison of the data of three groups of respondents (developers of educational programs and their curators at three levels of higher education). Approbation of the approach took place on the basis of the National Transport University (Kyiv, Ukraine). In total, 64 curators and developers of educational programs took part in the survey (this is 60% of educational programs of NTU). The results of the survey showed that educational program developers understand the importance of including the tasks of the United Nations Development Program in separate educational components or modules of disciplines in order to form relevant competencies in students. However, respondents noted the need to review educational programs and their components, as well as the educational process in the context of compliance with the goals of sustainable development and its ecologization. Practical implications. The results of this research will be used during the regular review of educational programs and their components at the National Transport University, and will also serve as a basis for further improvement of the concept of sustainable development of the NTU. The research data can be distributed to other universities. Also, the research results will be used in the project the Transformational Learning Network for Resilience – Enabling Ukrainian higher education to ensure a sustainable and robust reconstruction of (post-war) Ukraine (TransLearnN). The results of this study will contribute to the development of the program of sustainable development of universities in Ukraine. Value / Originality. The obtained results will make it possible to determine prospective directions for improving the educational process and educational programs of universities, taking into account the goals of sustainable development and trends in the ecologization of education.

The Role of Infrastructure Investment on Inclusive Growth and Human Development Index: Evidence from Emerging Economies

The paper examines the effect of infrastructure investment on the Human Development Index (HDI) score for five middle-income countries, namely Brazil, South Africa, Turkey, Mexico and Vietnam. The dynamic panel data model was used in the study. Data was sourced from the World Bank and the United Nations Development Programme focused on the prevalence and utilisation of five types of infrastructure in the countries mentioned above: electricity, water, sanitation, transport, telecommunications, and schools. The findings show that HDI is too narrow to be used as the main tool to measure human development and suggest that water and sanitation as well as the electrification of households were crucial infrastructures that had a positive impact on the HDI and be viewed as one type of infrastructure when researching the relationship between infrastructure investment and the HDI. The paper concluded and highlighted the need for infrastructure investors and policymakers to have a multi-dimensional approach to measuring the impact they would like to make. In this way, they would have more pronounced insights about which infrastructure they should invest in and how it will improve the wellbeing of society.

Determinants of Youth Participation in Community Development Projects in Limuru Subcounty, Kiambu County, Kenya

Government policy had been geared towards addressing youth unemployment and enhancing participation in development projects. However, the effect of youth involvement in community development projects had not been substantial, posing a challenge to the youth, government agencies, and the community at large. The study examined the determinants of youth participation in community development projects in Limuru subcounty. Specifically, it sought to determine the effects of socio-cultural factors, education level, information accessibility, and access to finance on youth participation in these projects. The study was underpinned by Arnstein’s theory of community participation. The descriptive research design targeted 38,410 youth in Limuru subcounty with a sample size of 395. Stratified sampling across five wards, proportionate sampling determined youths per ward. Simple random sampling selected participants. Data was collected through questionnaires and face-to-face interviews. Inferential statistics, Pearson correlation, and regression analysis were utilized. Research in Limuru subcounty reveals that socio-cultural factors have both positive and insignificant effects on youth participation in community projects (β = 0.491, p = 0.110). Higher education levels positively and significantly impact youth involvement (β = 0.568, p = 0.000). Information accessibility plays a positive and significant role (β = 0.071, p = 0.110), along with access to finance (β = 0.568, p = 0.000).The study concludes that youth education level influences involvement in community projects. Awareness campaigns and advocacy programs are key in promoting youth involvement in community projects. The study recommends that community leaders and stakeholders should consider the effect of youth attitudes, perceptions and religious affiliations when designing and implementing development initiatives. County and national development programs should focus on promoting a positive attitude towards loans among the youth, while providing guidance on managing collateral and securing funding.

Inclusive education in Sweden

Background and aim: Teachers’ positive attitudes towards inclusive education are taken to be critical to providing education that better meets pupils’ learning. Studies have therefore tried to clarify interaction between teachers’ attitudes and inclusive education. The present study reports data on teachers’ attitudes, self-efficacy and collaboration towards inclusive education in Sweden. Nation-wide data were collected from teachers before they joined a national professional development programme aimed at strengthening schools' competence in adapting teaching to the conditions and needs of pupils. Methods: Participants were 2,348 (51,6%) out of 4,553 targeted teachers that answered an online survey. The survey included three instruments: the Ohio State Teacher Efficacy Scale (OSTES), the Sentiments, Attitudes and Concerns about Inclusive Education – Revised (SACIE-R), and bespoke questions about teachers’ attitudes towards collegial learning (TACL). Mean values and correlations were assessed. Responses to an open question about teachers’ expectations ahead of starting their training programme were analyzed in NVivo, using word frequency analysis. Results: Three-quarters of respondents show overall positive responses towards adapting their teaching to the conditions and needs of pupils. However, almost two-thirds of teachers do also report significant concerns about their ability to do inclusive education well. Scores remained largely unaffected by public or private school ownership, nor did the affluence of school catchment areas affect teacher scores. Conclusions: The self-reported attitudes, self-efficacy and collaboration among teachers in Sweden towards adapting their teaching to the conditions and needs of pupils support positive research conclusions: although they do have concerns likely to be founded on professional considerations, teachers are by and large positive about meeting pupils’ learning needs.