bluuebunny/crossref_metadata_2025 huggingface dataset:
Process evaluation of the ‘Lafiyan Yara’ project on enhancing access to HIV testing services using existing community structures in Nigeria
Authors: Arije Olujide , Titus Rachel , Omisile Idowu , Dadi Aisha , Garba Danjuma , Godpower Omoregie , Anyanti Jennifer , Idogho Omokhudu , Okeke Emeka , Roebersen Carmen , Vrolings Eliane , Onayade Adedeji
Published: February 2024

Background

The Lafiyan Yara Project aimed to increase demand for HIV counselling, testing, treatment, and prevention services among pregnant women and children in Taraba State, Nigeria. Implemented from 2019 to 2021, the project utilized existing community structures, including traditional birth attendants, village health workers, and patent and proprietary medicine vendors, for mobilization. This study assessed the project’s activities, contributors, relevance, effectiveness, and efficiency.

Methods

The process evaluation was conducted using focus group discussions and key informant interviews with beneficiaries, community leaders, project staff, health facility personnel, and government officials. Data analysis employed framework analysis.

Results

The Lafiyan Yara project was reported to have achieved notable successes, including increased HIV testing rates among children and pregnant women, improved linkage to care services, reduced mother-to-child transmission of HIV, increased HIV/AIDS awareness and knowledge, and enhanced community engagement and support. Challenges identified included insufficient funding for community mobilizers, training needs for health workers, and inadequate availability of test kits at health facilities. Confidentiality and stigma issues arose during community mobilizations. A key lesson learned was the importance of a comprehensive HIV care approach, emphasizing testing and ensuring support for individuals testing positive.

Conclusions

The project’s approach of leveraging community structures to create demand for HIV services among women and children proved effective, provided proper linkage to care for those testing positive. Addressing stigma and involving husbands/fathers in the community approach are crucial for improving outcomes.

Trial registration

IPHOAU/12/1384.
Unveiling the unseen toll: exploring the impact of the Lebanese economic crisis on the health-seeking behaviors in a sample of patients with diabetes and hypertension
Authors: Cherfane Michelle , Boueri Myriam , Issa Elio , Abdallah Racha , Hamam Ali , Sbeity Kassem , Saad Anthony , Abi-Gerges Aniella
Published: February 2024

Background

Against the backdrop of Lebanon’s escalating multifaceted crisis which resulted in medication shortages for chronic diseases and unaffordable healthcare services, the current study endeavors to shed light on a critical yet overlooked facet of the Lebanese economic crisis– its profound impact on the health-seeking behaviors of patients with hypertension and diabetes mellitus.

Methods

An exploratory cross-sectional study based on an online questionnaire was conducted on 156 adult Lebanese citizens diagnosed medically with either hypertension or diabetes. We gathered sociodemographic characteristics and healthcare-related challenges faced during the economic crisis. We also assessed stress levels using the Depression Anxiety Stress Scale (DASS-21). Descriptive and bivariate analyses were done using SPSS version 26.

Results

The mean age of the population was 49.8 ± 17.7 years old, 51.6% were females and 48.4% were males, 29.7% had diabetes, 51.3% had hypertension and 19.0% had both diseases. Among all, 84.2% reported dissatisfaction with the current healthcare system, 31.6% reported changing their physician mainly because of unaffordable consultation fees (66%) or immigration of the physician (32%). Of those with hypertension and/or diabetes, less than 20% reported finding all their prescribed medications and 47% either modified or discontinued their treatment without seeking medical advice. In case of drug shortage, patients relied on stocked reserves (26%), alternative/generic medications (10%) and external sources for medication procurement such as relatives living abroad (41.7%), outsourcing suppliers (19.9%), dispensaries (19.6%) and NGOs (20.3%). All participants reported a high stress level (5.03/7) with a mean total DASS-21 score of 38.7 ± 35.8 that were attributed to August 4th Beirut port explosion (81.0%), global pandemic (81%), unstable political conditions (90.5%), economic crisis (96.8%), medication shortage (91.8%) and inability to access healthcare (74.1%). Higher sub-scores for anxiety, depression and total stress were insignificantly noted in participants with both hypertension and diabetes (p > 0.05).

Conclusion

Our findings explore how the economic crisis has taken its toll on almost all aspects of healthcare in a sample of patients with diabetes and hypertension in Lebanon. The drug shortage as well as disruptions in affordable healthcare access imposed several barriers to adequate adherence to treatment regimens and acted as important mental health stressors.
Prevalence, risk factors, and clinical characteristics of pulmonary embolism in patients with acute exacerbation of COPD in Plateau regions: a prospective cohort study
Authors: Yang Chenlu , Tuo Yajun , Shi Xuefeng , Duo Jie , Liu Xin , Zhang Fang , Feng Xiaokai
Published: February 2024

Background and objective

To investigate pulmonary thromboembolism (PE) in acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) patients in plateau regions, we performed a prospective cohort study to evaluate the prevalence, risk factors and clinical characteristics of PE in the cohort of hospitalized patients at high altitude.

Methods

We did a prospective study with a total of 636 AE-COPD patients in plateau regions. Demographic and clinical data, laboratory data, including ultrasound scans of the lower extremities and cardiac ultrasound, and computed tomographic pulmonary angiography (CTPA) variables were obtained, and comparisons were made between groups with and without PE. We also conducted logistic regression to explore the risk factors of PE.

Results

Of the 636 patients hospitalized with AE-COPD (age 67.0 ± 10.7 years, 445[70.0%] male), 188 patients developed PE (29.6% [95% CI: 26.0%, 33.1%]). Multivariable logistic regression showed that ethnic minorities, D-dimer > 1 mg/L, AST > 40 U/L, chest pain, cardiac insufficiency or respiratory failure, Padua score > 3, and DVT were associated with a higher probability of PE.

Conclusions

The prevalence of PE is high and those with a higher Padua score, the occurrence of deep venous thrombosis, higher neutrophil count, chest pain, cardiac insufficiency or respiratory failure, higher levels of AST, and a higher level of D-dimer had a higher risk of PE. The analysis of AE-COPD may help to provide more accurate screening for PE and improve clinical outcomes of patients with AE-COPD in plateau regions.
Illness perceptions in people with chronic and disabling non-specific neck pain seeking primary healthcare: a qualitative study
Authors: Kragting Maaike , Pool-Goudzwaard Annelies L. , Coppieters Michel W. , O’Sullivan Peter B. , Voogt Lennard
Published: February 2024

Background

Illness perceptions can affect the way people with musculoskeletal pain emotionally and behaviorally cope with their health condition. Understanding patients illness perceptions may help facilitate patient-centered care. The purpose of this study was to explore illness perceptions and the origin of those perceptions in people with chronic disabling non-specific neck pain seeking primary care.

Methods

A qualitative study using a deductive and inductive analytical approach was conducted in 20 people with persistent (> 3 months) and disabling (i.e., Neck Disability Index ≥ 15) neck pain. Using a semi-structured format, participants were interviewed about their illness perceptions according to Leventhal’s Common Sense Model. Purposive sampling and member checking were used to secure validity of study results.

Results

Participants reported multiple symptoms, thoughts and emotions related to their neck pain, which continuously required attention and action. They felt trapped within a complex multifactorial problem. Although some participants had a broader biopsychosocial perspective to understand their symptoms, a biomedical perspective was dominant in the labelling of their condition and their way of coping (e.g., limiting load, building strength and resilience, regaining mobility, keep moving and being meaningful). Their perceptions were strongly influenced by information from clinicians. Several participants indicated that they felt uncertain, because the information they received was contradictory or did not match their own experiences.

Conclusion

Most participants reported that understanding their pain was important to them and influenced how they coped with pain. Addressing this ‘sense making process’ is a prerequisite for providing patient-centered care.
Amelogenin-inspired peptide, calcium phosphate solution, fluoride and their synergistic effect on enamel biomimetic remineralization: an in vitro pH-cycling model
Authors: Sakr Aliaa H. , Nassif Mohammed Salah , El-Korashy Dalia I.
Published: February 2024

Background

Several methods were introduced for enamel biomimetic remineralization that utilize a biomimetic analogue to interact and absorb bioavailable calcium and phosphate ions and induce crystal nucleation on demineralized enamel. Amelogenin is the most predominant enamel matrix protein that is involved in enamel biomineralization. It plays a major role in developing the enamel’s hierarchical microstructure. Therefore, this study was conducted to evaluate the ability of an amelogenin-inspired peptide to promote the remineralization potential of fluoride and a supersaturated calcium phosphate solution in treating artificially induced enamel carious lesions under pH-cycling regimen.

Methods

Fifty enamel slices were prepared with a window (4*4 mm2 ) on the surface. Five samples were set as control healthy enamel and 45 samples were subjected to demineralization for 3 days. Another 5 samples were set as control demineralized enamel and 40 enamel samples were assigned into 8 experimental groups (n=5) (P/I, P/II, P/III, P/AS, NP/I, NP/II, NP/III and NP/AS) according to peptide treatment (peptide P or non-peptide NP) and remineralizing solution used (I; calcium phosphate solution, II; calcium phosphate fluoride solution, III; fluoride solution and AS; artificial saliva). Samples were then subjected to demineralization/remineralization cycles for 9 days. Samples in all experimental groups were evaluated using Raman spectroscopy for mineral content recovery percentage, microhardness and nanoindentation as healthy, demineralized enamel and after pH-cycling. Data were statistically analysed using two-way repeated measures Anova followed by Bonferroni-corrected post hoc test for pairwise multiple comparisons between groups. Statistical significance was set at p= 0.05. Additionally, XRD, FESEM and EDXS were used for crystal orientation, surface morphology and elemental analysis after pH-cycling.

Results

Nanocrystals clumped in a directional manner were detected in peptide-treated groups. P/II showed the highest significant mean values in mineral content recovery (63.31%), microhardness (268.81±6.52 VHN), elastic modulus (88.74±2.71 GPa), nanohardness (3.08±0.59 GPa) and the best crystal orientation with I002/I300 (1.87±0.08).

Conclusion

Despite pH changes, the tested peptide was capable of remineralizing enamel with ordered crystals. Moreover, the supplementary use of calcium phosphate fluoride solution with peptide granted an enhancement in enamel mechanical properties after remineralization.
Attractiveness and gender dynamics in surgical specialties: a comparative analysis of French medical graduates (2017–2022)
Authors: Saadé Saadé , Delafontaine Arnaud , Cattan Johann , Celanie Doris , Saiydoun Gabriel
Published: February 2024

Background

French medical graduates undertake a national examination at the end of their studies with a subsequent national ranking. Specialty is then chosen by each candidate according to their ranking. This study aims to describe the attractiveness of surgical specialties and the evolution of the male-female distribution among French medical graduates (FMG) from 2017 to 2022.

Methods

Our database included the candidates’ ranking, sex and choice of specialty from 2017 to 2022. It included all French medical graduates from 2017 to 2022 and all French medical schools. A linear regression was performed to predict future trends. Dependent variables were mean rankings and the percentage of women. The independent variable was year of application. A Pearson correlation was performed to examine any relationship with mean workweek.

Results

A total number of 5270 residents chose a surgical programme between 2017 and 2022. The number of residents who were assigned their desired surgical programme held stable at 878 surgical residents per year. Plastic and reconstructive surgery remained the most frequently chosen surgical programme. Thoracic and cardiovascular surgery was the least frequently chosen surgical programme between 2017 and 2022. The mean ranking for a candidate choosing a surgical programme rose significantly by 9% from 2017 to 2022 (p < 0.01). Neurosurgery exhibited the greatest fall as a surgical specialty as its rankings decreased by 163.6% (p < 0.01). Maxillo-facial surgery was the only specialty with a statistically significant increase in its rankings by 35.9% (p < 0.05). The overall proportion of women was 51.1%. Obstetrics-and-gynecology was the highest represented specialty among female candidates, with a mean of 83.9% of women. Orthopedic surgery was the lowest represented, being composed of a mean of 28.6% of women. The number of female surgical residents increased significantly over the six-year period, by 7.6% (p < 0.01).

Conclusions

More and more medical school graduates decide not to choose surgery for their residency programme. Some specialties continue to be attractive while many are losing their appeal. While there does appear to be progress towards gender equity, further investigation is necessary to assess its actual implementation.
Adapting the Donabedian model in undergraduate nursing education: a modified Delphi study
Authors: Ghofrani Marjan , Valizadeh Leila , Zamanzadeh Vahid , Ghahramanian Akram , Janati Ali , Taleghani Fariba
Published: February 2024

Background

Donabedian conceptual and multidimensional framework has been used in several studies in an educational context. In this study, we aimed to adapt the Donabedian three-component model (structure, process, and outcome) in undergraduate nursing education. This conceptual framework provides a comprehensive image of nursing education institutions and can help to evaluate institutions by measuring different aspects of their performance. A comprehensive understanding of the various elements of an educational institution helps to develop a complete, appropriate relevant set of performance indicators.

Methods

This was a modified Delphi study. It had three rounds. The expert panel consisted of nursing faculty members and nursing Ph.D. students. In the first round, a questionnaire was designed based on interviews, focus groups, and a literature review. Experts rated their agreement with each element on a 5-point Likert scale in rounds two and three. The consensus level was set as 75%. The stability between rounds was also determined by calculating kappa coefficients. One Sample T-Test was also calculated for new items in round three.

Results

All 55 items of the questionnaire were confirmed in the second round based on the consensus percentage of 75. Five new items were added to the third round based on comments in round two. Eventually, all elements except one were confirmed according to the consensus level, kappa values, means, and One-Sample T-Test in round three. The structure's key elements include staff (academic and non-academic); equipment; guidelines; resources and facilities; and students’ demographics and characteristics. Process key elements include communication; education; evaluation; cooperation; and consultation. Outcome key elements include knowledge development; nursing image; alumni’s outcome; students’ outcome; related medical centers’ performance; accreditation and evaluation results; and satisfaction.

Conclusions

Different elements of a nursing education institution at the bachelor's level were determined. The results of this study can help related bodies to develop and implement a comprehensive and systematic evaluation. These results can also be a basis for making this model useful in other nursing courses or education in other fields.
Alpha-sitosterol: a new antiviral agent produced by Streptomyces misakiensis and its potential activity against Newcastle disease virus
Authors: Abdelaziz Rewan , Tartor Yasmine H. , Barakat Ahmed B. , EL-Didamony Gamal , Gado Marwa M. , Zaki Mohamed Samir A. , Eid Refaat A. , El-Samadony Hanaa A.
Published: February 2024

Background

Newcastle Disease Virus (NDV) causes severe economic losses in the poultry industry worldwide. Hence, this study aimed to discover a novel bioactive antiviral agent for controlling NDV. Streptomyces misakiensis was isolated from Egyptian soil and its secondary metabolites were identified using infrared spectroscopy (IR), gas chromatography–mass spectrometry (GC–MS), and nuclear magnetic resonance (NMR) spectroscopy. The inhibitory activity of bioactive metabolite against NDV were examined. Three experimental groups of 10-day-old specific pathogen-free embryonated chicken eggs (SPF-ECEs), including the bioactive metabolite control group, NDV control positive group, and α-sitosterol and NDV mixture-treated group were inoculated.

Results

α-sitosterol (Ethyl-6-methylheptan-2-yl]-10,13-dimethyl-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol), a secondary metabolite of S. misakiensis, completely inhibited hemagglutination (HA) activity of the NDV strain. The HA activity of the NDV strain was 8 log2 and 9 log2 for 0.5 and 0.75% RBCs, respectively. The NDV HA activity for the two concentrations of RBCs was significantly (P < 0.0001) inhibited after α-sitosterol treatment. There was a significant (P < 0.0001) decrease in the log 2 of HA activity, with values of − 0.500 (75%, chicken RBCs) before inoculation in SPF-ECEs and − 1.161 (50%, RBCs) and − 1.403 (75%, RBCs) following SPF-ECE inoculation. Compared to ECEs inoculated with NDV alone, the α-sitosterol-treated group showed improvement in histological lesion ratings for chorioallantoic membranes (CAM) and hepatic tissues. The CAM of the α-sitosterol- inoculated SPF-ECEs was preserved. The epithelial and stromal layers were noticeably thicker with extensive hemorrhages, clogged vasculatures, and certain inflammatory cells in the stroma layer in the NDV group. However, mild edema and inflammatory cell infiltration were observed in the CAM of the treated group. ECEs inoculated with α-sitosterol alone showed normal histology of the hepatic acini, central veins, and portal triads. Severe degenerative alterations, including steatosis, clogged sinusoids, and central veins, were observed in ECEs inoculated with NDV. Mild hepatic degenerative alterations, with perivascular round cell infiltration, were observed in the treated group.

Conclusion

To the best of our knowledge, this is the first study to highlight that the potentially bioactive secondary metabolite, α-sitosterol, belonging to the terpene family, has the potential to be a biological weapon against virulent NDV. It could be used for the development of innovative antiviral drugs to control NDV after further clinical investigation.
Food sufficiency status and sleep outcomes in older adults: the National Health and Aging Trends Study (NHATS)
Authors: Flores Ashley C. , Sarpong Christopher , Dou Nan , Na Muzi
Published: February 2024

Background

Studies investigating the relationship between food insecurity and sleep among older populations are limited. This study aimed to cross-sectionally examine the associations between food sufficiency status and sleep outcomes in a nationally representative sample of older adults.

Methods

Our study included 1,665 older adults (≥ 65 years), using data from the 2013 and 2014 National Health and Aging Trends Study (NHATS). Food insufficiency was determined via participants’ experience and utilization of food assistance programs (FAP). Sleep outcomes, including nighttime and total sleep hours, sleep latency, and sleep quality, were derived from self-reported data. Multivariable linear regression and logistic regression models were used to estimate the associations between food sufficiency status and sleep outcomes.

Results

In 2013–2014, 86.1% of older adults were classified as food sufficient without FAP, 9.85% as food sufficient with FAP, and 4.08% as food insufficient. Adjusting for sociodemographic characteristics, food sufficient older adults with FAP reported more total sleep hours (𝛽 = 0.31, 95% CI: -0.02, 0.64) than those participants who are food sufficient without FAP. Further adjusting for health factors, food sufficient participants with FAP had more nighttime sleep hours and greater total sleep hours compared to those participants food sufficient without FAP. Compared to those deemed as food sufficient without FAP, food sufficient participants with FAP had lower odds of having longer sleep latency (OR = 0.50, 95% CI: 0.28, 0.89), after further adjusting for physical function performance.

Conclusions

Among older adults, food sufficiency with FAP is associated with greater total sleep hours, greater nighttime sleep hours, and lower odds of longer sleep latency. Our findings may help inform nutrition food assistance programs targeting older populations.
Diversity of astroviruses in wild animals in Yunnan province, China
Authors: Huang Xingyu , Hou Junjie , Le Xiang , Hou Yutong , Yang Lingsi , Li Qian , Wang Binghui , Xia Xueshan
Published: February 2024

Background

Astroviruses (AstVs) are single-stranded RNA viruses that have been detected in a wide range of mammals and birds. They are associated with numerous interspecies transmissions and viral recombination events, posing a threat to human and animal health.

Methods

We collected 1,333 samples from wild animals, including bats, rodents, wild boars, and birds, from various states and cities in the Yunnan Province, China, between 2020 and 2023 to investigate the presence of AstVs. AstVs were detected using a polymerase chain reaction targeting the RdRp gene. Finally, the Molecular Evolutionary Genetics Analysis software was used to construct the phylogenetic tree.

Results

The overall positivity rate for AstVs was 7.12% in four species, indicating their widespread occurrence in the region. High genetic diversity among AstVs was observed in different animal species, suggesting the potential for interspecies transmission, particularly among rodents and birds. Additionally, we identified a novel AstV strain and, for the first time, provided information on the presence of bastroviruses in Yunnan, China.

Conclusions

The widespread distribution and high genetic diversity of AstVs, along with the observed potential for interspecies transmission, highlight the importance of further investigation and surveillance in the region. The findings emphasize the need for increased attention to AstVs and their potential impact on human and animal health in Yunnan and other regions.
Differential pulmonary toxicity and autoantibody formation in genetically distinct mouse strains following combined exposure to silica and diesel exhaust particles
Authors: Janssen Lisa MF , Lemaire Frauke , Marain Nora Fopke , Ronsmans Steven , Heylen Natasja , Vanstapel Arno , Velde Greetje Vande , Vanoirbeek Jeroen AJ , Pollard Kenneth Michael , Ghosh Manosij , Hoet Peter HM
Published: February 2024

Background

Inhalation of airborne particulate matter, such as silica and diesel exhaust particles, poses serious long-term respiratory and systemic health risks. Silica exposure can lead to silicosis and systemic autoimmune diseases, while DEP exposure is linked to asthma and cancer. Combined exposure to silica and DEP, common in mining, may have more severe effects. This study investigates the separate and combined effects of occupational-level silica and ambient-level DEP on lung injury, inflammation, and autoantibody formation in two genetically distinct mouse strains, thereby aiming at understanding the interplay between genetic susceptibility, particulate exposure, and disease outcomes. Silica and diesel exhaust particles were administered to mice via oropharyngeal aspiration. Assessments of lung injury and host response included in vivo lung micro-computed tomography, lung function tests, bronchoalveolar lavage fluid analysis including inflammatory cytokines and antinuclear antibodies, and histopathology with particle colocalization.

Results

The findings highlight the distinct effects of silica and diesel exhaust particles (DEP) on lung injury, inflammation, and autoantibody formation in C57BL/6J and NOD/ShiLtJ mice. Silica exposure elicited a well-established inflammatory response marked by inflammatory infiltrates, release of cytokines, and chemokines, alongside mild fibrosis, indicated by collagen deposition in the lungs of both C57BL/6J and NOD/ShilLtJ mice. Notably, these strains exhibited divergent responses in terms of respiratory function and lung volumes, as assessed through micro-computed tomography. Additionally, silica exposure induced airway hyperreactivity and elevated antinuclear antibody levels in bronchoalveolar lavage fluid, particularly prominent in NOD/ShiLtJ mice. Moreover, antinuclear antibodies correlated with extent of lung inflammation in NOD/ShiLTJ mice. Lung tissue analysis revealed DEP loaded macrophages and co-localization of silica and DEP particles. However, aside from contributing to airway hyperreactivity specifically in NOD/ShiLtJ mice, the ambient-level DEP did not significantly amplify the effects induced by silica. There was no evidence of synergistic or additive interaction between these specific doses of silica and DEP in inducing lung damage or inflammation in either of the mouse strains.

Conclusion

Mouse strain variations exerted a substantial influence on the development of silica induced lung alterations. Furthermore, the additional impact of ambient-level DEP on these silica-induced effects was minimal.
Evidence on the impact of community health workers in the prevention, identification, and management of undernutrition amongst children under the age of five in conflict-affected or fragile settings: a systematic literature review
Authors: Bridge Rachel , Lin Tracy Kuo
Published: February 2024

Background

Malnutrition, specifically undernutrition, is a significant global challenge that contributes to nearly half of deaths in children under the age of five. The burden of undernutrition is disproportionately borne by conflict-affected, fragile settings (CAFS); children living in a conflict zone being more than twice as likely to suffer from malnourishment. Community health worker (CHW) models have been employed in CAFS to improve healthcare coverage and identify and treat illnesses. However, there lacks systematic evidence on the impact of CHW models in preventing, identifying, and managing child undernutrition in CAFS. We conducted this review to systematically evaluate evidence of CHW models in preventing, identifying, and managing undernutrition in children under the age of five in CAFS.

Methodology

This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. The search strategy was developed using the Population-Intervention-Comparisons-Outcomes-Setting framework as a guide. Searches were performed using Ovid online database search platform, searching the databases of Ovid MEDLINE(R), COCHRANE, Embase Classic, Embase, Econlit, Global Health, SCOPUS, and Social Policy and Practice. Peer-reviewed publications were eligible for inclusion if they evaluated an intervention using a CHW model that aims to prevent, identify, or manage some form of undernutrition in children under five in a CAFS.

Results

We identified 25 studies—spanning 10 countries—that were included in the systematic review. CHW models were implemented alongside a variety of interventions, including behaviour change communication, supplementary foods, nutrition counselling, and integrated community health programmes. Key barriers in implementing successful CHW models include disruption of programmes due to active conflict, states of emergency, militancy, or political unrest; weak links between the community-based interventions and public health system; weak health system capacity that impeded referral and follow-ups; and cost of care and care-seeking. Key facilitators include CHWs’ connection to the community, close proximity of programmes to the community, supervision, and investment in high quality training and tools.

Conclusions

The findings suggest that CHW models may be effective, cost-effective, acceptable, feasible, and scalable in the prevention, identification, and management child undernutrition in CAFS. The study findings also confirmed a need for greater evidence in the field. These findings may inform policymaking, programme implementation, and design to strengthen best practices for CHW models addressing child undernutrition in CAFS.
Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer
Authors: Li Keyu , Xue Wenhua , Lu Zhihua , Wang Suo , Zheng Jiayao , Lu Kuangyi , Li Ming , Zong Yang , Xu Feng , Dai Jiamin , Yang Yang , Sun Jinbing
Published: February 2024

Background

Hematological metastasis has been recognized as a crucial factor contributing to the high rates of metastasis and mortality observed in colorectal cancer (CRC). Notably, exosomes derived from cancer cells participate in the formation of CRC pre-metastatic niches; however, the mechanisms underlying their effects are largely unknown. While our preliminary research revealed the role of exosome-derived disintegrin and metalloproteinase 17 (ADAM17) in the early stages of CRC metastasis, the role of exosomal ADAM17 in CRC hematogenous metastasis remains unclear.

Methods

In the present study, we isolated and purified exosomes using ultracentrifugation and identified exosomal proteins through quantitative mass spectrometry. In vitro, co-culture assays were conducted to evaluate the impact of exosomal ADAM17 on the permeability of the blood vessel endothelium. Vascular endothelial cell resistance, the cell index, membrane protein separation, flow cytometry, and immunofluorescence were employed to investigate the mechanisms underlying exosomal ADAM17-induced vascular permeability. Additionally, a mouse model was established to elucidate the role of exosomal ADAM17 in the modulation of blood vessel permeability and pre-metastatic niche formation in vivo.

Results

Our clinical data indicated that ADAM17 derived from the circulating exosomes of patients with CRC could serve as a blood-based biomarker for predicting metastasis. The CRC-derived exosomal ADAM17 targeted vascular endothelial cells, thus enhancing vascular permeability by influencing vascular endothelial cadherin cell membrane localization. Moreover, exosomal ADAM17 mediated the formation of a pre-metastatic niche in nude mice by inducing vascular leakage, thereby promoting CRC metastasis. Nonetheless, ADAM17 selective inhibitors effectively reduced CRC metastasis in vivo.

Conclusions

Our results suggest that exosomal ADAM17 plays a pivotal role in the hematogenous metastasis of CRC. Thus, this protein may serve as a valuable blood-based biomarker and potential drug target for CRC metastasis intervention.
Use of Remdesivir in children with COVID-19: report of an Italian multicenter study
Authors: Romani Lorenza , Roversi Marco , Bernardi Stefania , Venturini Elisabetta , Garazzino Silvia , Donà Daniele , Krzysztofiak Andrzej , Montagnani Carlotta , Funiciello Elisa , Calò Carducci Francesca Ippolita , Marabotto Caterina , Castagnola Elio , Salvini Filippo , Lancella Laura , Lo Vecchio Andrea , Galli Luisa , Castelli Gattinara Guido ,   Italian Society of Pediatric Infectious Diseases (SITIP)
Published: February 2024

Background

COVID-19 is generally milder in children than in adults, however severe infection has been described in some patients. Few data are available on use of Remdesivir (RDV) in children, as most clinical trials focused on adult patients. We report a multicenter study conducted in 10 Italian Hospitals to investigate the safety of RDV in children affected by COVID-19.

Methods

We collected the clinical data of children with COVID-19 treated with RDV between March 2020 and February 2022 in 10 Italian hospitals. Clinical data were compared according to a duration of RDV therapy more or less than 5 days. Linear regression model was used to determine the association of significant variables from the bivariate analysis to the duration of RDV therapy.

Results

A total of 50 patients were included, with a median age of 12.8 years. Many patients had at least one comorbidity (78%), mostly obesity. Symptoms were fever (88%), cough (74%) and dyspnea (68%). Most patients were diagnosed with pneumonia of either viral and/or bacterial etiology. Blood test showed leukopenia in 66% and increased C-reactive protein (CRP) levels in 63% of cases. Thirty-six patients received RDV for 5 days, nine patients up to 10 days. Most children who received RDV longer were admitted to the PICU (67%). Treatment with RDV was well tolerated with rare side effects: bradycardia was recorded in 6% of cases, solved in less than 24 h after discontinuation. A mild elevation of transaminases was observed in 26% of cases, however for the 8%, it was still detected before the RDV administration. Therefore, in these cases, we could not establish if it was caused by COVID-19, RDV o both. Patients who received RDV for more than 5 days waited longer for its administration after pneumonia diagnosis. The presence of comorbidities and the duration of O2 administration significantly correlated with the duration of RDV therapy at the linear regression analysis.

Conclusion

Our experience indicates that RDV against SARS-CoV-2 is safe and well-tolerated in pediatric populations at high risk of developing severe COVID-19. Our data suggest that delaying RDV therapy after diagnosis of pneumonia may be associated with a longer duration of antiviral therapy, especially in patients with comorbidities.
Effectiveness and cost-effectiveness of a transdiagnostic intervention for alcohol misuse and psychological distress in humanitarian settings: study protocol for a randomised controlled trial in Uganda
Authors: van der Boor Catharina F. , Taban Dalili , Tol Wietse A. , Akellot Josephine , Neuman Melissa , Weiss Helen A. , Greco Giulia , Vassall Anna , May Carl , Nadkarni Abhijit , Kinyanda Eugene , Roberts Bayard , Fuhr Daniela C.
Published: February 2024

Background

The war in South Sudan has displaced more than four million people, with Uganda hosting the largest number of South Sudanese refugees. Research in Uganda has shown elevated levels of alcohol misuse and psychological distress among these refugees. The World Health Organization (WHO) has developed a trans-diagnostic scalable psychological intervention called Problem Management Plus (PM +) to reduce psychological distress among populations exposed to adversities. Our study aims to evaluate the effectiveness and cost-effectiveness of the CHANGE intervention, which builds on PM + , to also address alcohol misuse through problem-solving therapy and selected behavioural strategies for dealing with alcohol use disorders. We hypothesise that the CHANGE intervention together with enhanced usual care (EUC) will be superior to EUC alone in increasing the percentage of days abstinent.

Methods

A parallel-arm individually randomised controlled trial will be conducted in the Rhino Camp and Imvepi settlements in Uganda. Five hundred adult male South Sudanese refugees with (i) elevated levels of alcohol use (between 8 and 20 on the Alcohol Use Disorder Identification Test [AUDIT]); and (ii) psychological distress (> 16 on the Kessler Psychological Distress Scale) will be randomly assigned 1:1 to EUC or CHANGE and EUC. CHANGE will be delivered by lay healthcare providers over 6 weeks. Outcomes will be assessed at 3 and 12 months post-randomisation. The primary outcome is the percentage of days abstinent, measured by the timeline follow-back measure at 3 months. Secondary outcomes include percentage of days abstinent at 12 months and alcohol misuse (measured by the AUDIT), psychological distress (i.e. depression, anxiety, posttraumatic stress disorder), functional disability, perpetration of intimate partner violence, and health economic indicators at 3 and 12 months. A mixed-methods process evaluation will investigate competency, dose, fidelity, feasibility, and acceptability. Primary analyses will be intention-to-treat.

Discussion

CHANGE aims to address alcohol misuse and psychological distress with male refugees in a humanitarian setting. If it is proven to be effective, it can help fill an important under-researched gap in humanitarian service delivery.

Trial registration

ISRCTN ISRCTN10360385. Registered on 30 January 2023.
Improvements in lung function following vitamin C supplementation to pregnant smokers are associated with buccal DNA methylation at 5 years of age
Authors: Shorey-Kendrick Lyndsey E. , McEvoy Cindy T. , Milner Kristin , Harris Julia , Brownsberger Julie , Tepper Robert S. , Park Byung , Gao Lina , Vu Annette , Morris Cynthia D. , Spindel Eliot R.
Published: February 2024

Background

We previously reported in the “Vitamin C to Decrease the Effects of Smoking in Pregnancy on Infant Lung Function” randomized clinical trial (RCT) that vitamin C (500 mg/day) supplementation to pregnant smokers is associated with improved respiratory outcomes that persist through 5 years of age. The objective of this study was to assess whether buccal cell DNA methylation (DNAm), as a surrogate for airway epithelium, is associated with vitamin C supplementation, improved lung function, and decreased occurrence of wheeze.

Methods

We conducted epigenome-wide association studies (EWAS) using Infinium MethylationEPIC arrays and buccal DNAm from 158 subjects (80 placebo; 78 vitamin C) with pulmonary function testing (PFT) performed at the 5-year visit. EWAS were performed on (1) vitamin C treatment, (2) forced expiratory flow between 25 and 75% of expired volume (FEF25–75), and (3) offspring wheeze. Models were adjusted for sex, race, study site, gestational age at randomization (≤ OR > 18 weeks), proportion of epithelial cells, and latent covariates in addition to child length at PFT in EWAS for FEF25–75. We considered FDR p < 0.05 as genome-wide significant and nominal p < 0.001 as candidates for downstream analyses. Buccal DNAm measured in a subset of subjects at birth and near 1 year of age was used to determine whether DNAm signatures originated in utero, or emerged with age.

Results

Vitamin C treatment was associated with 457 FDR significant (q < 0.05) differentially methylated CpGs (DMCs; 236 hypermethylated; 221 hypomethylated) and 53 differentially methylated regions (DMRs; 26 hyper; 27 hypo) at 5 years of age. FEF25–75 was associated with one FDR significant DMC (cg05814800), 1,468 candidate DMCs (p < 0.001), and 44 DMRs. Current wheeze was associated with 0 FDR-DMCs, 782 candidate DMCs, and 19 DMRs (p < 0.001). In 365/457 vitamin C FDR significant DMCs at 5 years of age, there was no significant interaction between time and treatment.

Conclusions

Vitamin C supplementation to pregnant smokers is associated with buccal DNA methylation in offspring at 5 years of age, and most methylation signatures appear to be persistent from the prenatal period. Buccal methylation at 5 years was also associated with current lung function and occurrence of wheeze, and these functionally associated loci are enriched for vitamin C associated loci.

Clinical trial registration ClinicalTrials.gov, NCT01723696 and NCT03203603.
Prediction of methylation status using WGS data of plasma cfDNA for multi-cancer early detection (MCED)
Authors: Cui Pin , Zhou Xiaozhou , Xu Shu , He Weihuang , Huang Guozeng , Xiong Yong , Zhang Chuxin , Chang Tingmin , Feng Mingji , Lai Hanming , Pan Yi
Published: February 2024

Background

Cell-free DNA (cfDNA) contains a large amount of molecular information that can be used for multi-cancer early detection (MCED), including changes in epigenetic status of cfDNA, such as cfDNA fragmentation profile. The fragmentation of cfDNA is non-random and may be related to cfDNA methylation. This study provides clinical evidence for the feasibility of inferring cfDNA methylation levels based on cfDNA fragmentation patterns. We performed whole-genome bisulfite sequencing and whole-genome sequencing (WGS) on both healthy individuals and cancer patients. Using the information of whole-genome methylation levels, we investigated cytosine–phosphate–guanine (CpG) cleavage profile and validated the method of predicting the methylation level of individual CpG sites using WGS data.

Results

We conducted CpG cleavage profile biomarker analysis on data from both healthy individuals and cancer patients. We obtained unique or shared potential biomarkers for each group and built models accordingly. The modeling results proved the feasibility to predict the methylation status of single CpG sites in cfDNA using cleavage profile model from WGS data.

Conclusion

By combining cfDNA cleavage profile of CpG sites with machine learning algorithms, we have identified specific CpG cleavage profile as biomarkers to predict the methylation status of individual CpG sites. Therefore, methylation profile, a widely used epigenetic biomarker, can be obtained from a single WGS assay for MCED.
Coronary chronic total occlusion on coronary CT angiography: what radiologists should know?
Authors: Xu Wei , Ma Junfeng , Chen Yiwen , Zhou Fan , Zhou Changsheng , Zhang Long Jiang
Published: February 2024

Coronary chronic total occlusion (CTO) often occurs in patients with obstructive coronary artery disease, which remains one of the greatest challenges for interventional cardiologists. Coronary computed tomography angiography (CCTA) with its emerging post-processing techniques can provide a detailed assessment of CTO lesions before percutaneous coronary intervention (PCI), playing an important role in the clinical management of CTO PCI, from early diagnosis, pre-procedural outcome prediction, the crossing algorithm planning, intraprocedural guidance, and finally post-procedural assessment and follow-up. In addition, the feasibility of CT perfusion (CTP) in patients with CTO has been validated. Combined CCTA and CTP have the great potential to be the one-stop-shop imaging modality for assessing both anatomy and function of CTO lesions. This review aims to make radiologists understand the role of CCTA in the diagnosis and assessment of CTO lesions, thus assisting interventionalists in optimizing CTO PCI crossing strategies with the expertise of radiologists.

Critical relevance statementThe anatomical features of CTO on CCTA can reveal the complexity of CTO lesions and are associated with CTO PCI outcome, thus helping interventionalists optimize CTO PCI crossing strategies.

Key points• CTO is the common lesion in invasive coronary angiography, and CTO PCI is technically difficult and its success rate is relatively low.

• Length, collaterals, and attenuation-related signs can help distinguish CTO from subtotal occlusion.

• The anatomical features of CTO lesions can help grade the difficulty of CTO PCI and predict procedural outcomes and long-term outcomes of CTO PCI.

• The real-time fusion of CCTA with fluoroscopic angiography can be applied in highly complicated CTO lesions.

• After CTO PCI, CCTA can help guide a second CTO PCI re-entry or follow up stent patency.

Graphical Abstract
Timing of preventive behavior in the case of a new and evolving health risk: the case of COVID-19 vaccination
Authors: Gupta Deeksha , Rudisill Caroline
Published: February 2024

Background

Time preferences for preventive behavior under novel risks and uncertain contexts may differ from timing preferences related to familiar risks. Therefore, it is crucial to examine drivers of preventative health behavior timing in light of new health risks. Using the case of COVID-19, we examine factors affecting vaccination timing plans when vaccines were widely available in the European Union (EU).

Methods

We use data from the Flash Eurobarometer 494 survey (May 21–26, 2021), which collected information on EU residents’ attitudes towards COVID-19 vaccinations. We also use the ‘Our World in Data’ vaccination database for country-level COVID-19 vaccination rates. Probit regressions were conducted to determine how local vaccination rates, trust in information sources, social norms, vaccine safety beliefs, and risk understanding affected the probability of COVID-19 vaccination delay.

Results

Of total participants (n = 26,106), 9,063 (34.7%) were vaccinated, 7,114 (27.3%) wanted to get vaccinated as soon as possible, 5,168 (19.8%) wanted to delay vaccination and 2,962 (11.4%) resisted vaccination. Participants were more likely to delay COVID-19 vaccination if they lived in a country with lower vaccination prevalence, trusted online social networks, family, friends, and colleagues for vaccination information, were eager to follow vaccination-related social norms, expressed vaccine safety concerns, and understood the risk of catching COVID-19 without a vaccine to be lower.

Conclusions

Results from the study contribute to understanding important factors that predict timing of vaccination plans. These findings can also contribute to the wider knowledge base about timing of preventive behavior uptake in novel risk contexts.
Impact and policy supporting Thailand innovation driven enterprise: orchestrating university innovation and entrepreneurship ecosystem with public and private stakeholders
Authors: Thawesaengskulthai Natcha , Chatmarathong Awirut , Koiwanit Jarotwan
Published: February 2024

This research paper aims to investigate the impediments faced by innovation-driven enterprises in Thailand and to explore the current measures, policies, and mechanisms related to innovation-driven enterprises (IDEs)’ development both domestically and internationally. The study encompasses a comprehensive approach, including an analysis of an innovation entrepreneur database comprising 320 investors and 883 IDEs. Moreover, semi-structure in-depth interviews were conducted with three investors, twenty-two IDEs’ founders, eight executives, and experts from various sectors, including government, university incubators, and the private sector in Thailand. Through this multifaceted investigation, this paper sheds light on the key factors that hinder the success of IDEs in Thailand, which primarily revolve around the quality of entrepreneurs (Team), Product and Market Fit, and Support. These factors collectively impact the depth of knowledge, business incubation, acceleration programs, and the effectiveness of laws, measures, and policies in supporting innovation capability development within IDEs. In addition, this paper presents a framework for Thailand’s IDEs hub, facilitating the connection between the university's innovation and entrepreneurship ecosystem with public and private stakeholders. This framework serves as a mechanism to address the identified hindrances and foster a conducive environment for IDEs development. To address the obstacles, this paper proposes three crucial strategies, namely, (1) talent management, (2) ease of doing scaleup, and (3) availability of funding. These strategies are envisioned to counteract the identified challenges and can be effectively implemented through an operating model and practical working procedures tailored to suit the specific context of Thailand.