bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of vision impairment, diabetic retinopathy and disability in adults 50+ in the occupied Palestinian territories
Authors: Mikki Nahed , McCormick Ian , Mactaggart Islay
Published: September 2024

The Rapid Assessment of Avoidable Blindness methodology is a population-based survey of vision impairment among the population 50 and above, with optional modules on diabetes, diabetic retinopathy and disability. The first Rapid Assessment of Avoidable Blindness study in the occupied Palestinian territories (oPt) was conducted in 2008. Prevalence of blindness (50+) was 3.4%. 80% of blindness was avoidable. Between July 2018 and April 2019, we completed a nationally-representative follow up survey in oPt using the Rapid Assessment of Avoidable Blindness methodology including the optional modules. We tested distance visual acuity (presenting and pinhole) using a bespoke mobile data collection application. 4223 Palestinians aged 50 years and above were enumerated, of whom 3847 participated (response rate 91.1%). Prevalence of any vision impairment (presenting vision impairment <6/12 in the better seeing eye), blindness (<3/60), severe vision impairment (<6/60 but ≥3/60), moderate vision impairment (<6/18 but ≥6/60) and mild vision impairment (<6/12 but ≥6/18) were 25.8% (95% confidence interval [CI] 23.8–27.8%), 2.6% (1.9–3.2%), 1.4% (1.0–1.8%), 10.2% (9.1–11.2%) and 11.6% (10.3–12.8%), respectively. Avoidable causes of poor vision accounted for 82.4% of blindness, 83.3% of severe vision impairment, 82.0% of moderate vision impairment and 90.2% of mild vision impairment. Diabetes prevalence (reported or suspected based on random blood glucose ≥200 milligrams/decilitre) was 33.8% (32.1–35.5). Half of diabetes participants had diabetic retinopathy and/or maculopathy. Prevalence of disability (reported functional limitations) was 23.8% (21.0–26.5), and higher in women than men. The prevalence of vision impairment and blindness in oPt compared with 2008 was similar. Prevalence of diabetes, diabetic retinopathy and disability were all high, highlighting key areas for public health prioritization among older adults in oPt.
Impacts of climate change on diarrhoeal disease hospitalisations: How does the global warming targets of 1.5–2°C affect Dhaka, Bangladesh?
Authors: Haque Farhana , Lampe Fiona C. , Hajat Shakoor , Stavrianaki Katerina , Hasan S. M. Tafsir , Faruque A. S. G. , Ahmed Tahmeed , Jubayer Shamim , Kelman Ilan
Published: September 2024

Dhaka is one of the world’s densely populated cities and faces significant public health challenges including high burden of diarrhoeal diseases. Climate change is intensifying existing environmental problems including urban heat island effect and poor water quality. While numerous epidemiological studies have linked meteorological factors to diarrhoeal diseases in Bangladesh, assessment of the impacts of future climate change on diarrhoeal diseases is scarce. We provide the assessment of climate change impacts on diarrhoeal disease in Dhaka and project future health risks under climate change scenarios. About 3 million acute diarrhoea cases presenting to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (icddr,b) during 1981–2010 were linked to daily temperature, rainfall and humidity and association investigated using time series adapted negative binomial regression models employing constrained distributed lag linear models. The findings were applied to climate projections to estimate future risks of diarrhoea under various global warming scenarios. There was a significantly raised risk of diarrhoea hospitalisation in all ages with daily mean temperature (RR: 3.4, 95% CI: 3.0–3.7) after controlling for the confounding effects of heavy rainfall, humidity, autocorrelations, day of the week effect, long-term time, and seasonal trends. Using the incidence rate ratio (IRR) of 1.034, temperature increases based on the global warming targets of 1.5–2°C could result in an increase of diarrhoea hospitalisations by 4.5–7.4% in all age groups by the 2100s. These effects were more pronounced among <5 children where the predicted temperature increases could raise diarrhoea hospitalisation by 5.7% - 9.4%. Diarrhoea hospitalisation will increase significantly in Dhaka even if the global warming targets adopted by the Paris Agreement is reached. This underscores the importance of preparing the city for management and prevention of diarrhoeal diseases.
Development and deployment of a solid oral amphotericin B dosage form to treat visceral leishmaniasis within a pediatric population
Authors: Wasan Kishor M.
Published: September 2024

Visceral leishmaniasis (VL) is a severe and potentially fatal infection, with over 90% of reported cases occurring in East African countries including Chad, Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan, and Uganda, affecting mainly impoverished individuals, and creating a significant economic burden. Currently, the intravenous single-dose liposomal amphotericin B is the first choice for the treatment of VL. Recently, WHO and DNDi have suggested a combination of intravenous liposomal amphotericin B and oral miltefosine as a potential approach to treat VL. However, miltefosine availability is uncertain, and its side effects frequently cause treatment to be discontinued. Furthermore, due to the difficult route of liposomal amphotericin B administration by intravenous infusion, the lack of formulation’s tropical stability, accessibility, injection toxicity, and cost have prevented this injectable formulation of amphotericin B from reaching the most infected populations, particularly the pediatric population. To solve this problem, the development of a solid oral amphotericin B formulation that is cost-effective, safe, tropically stable, and easy to swallow, making it more accessible to children, particularly in rural communities having limited access to medical clinics or trained healthcare professionals is imperative. This viewpoint will discuss the opportunities and challenges of developing an oral amphotericin B formulation for a pediatric population.
Stable introduction of Wolbachia wPip into invasive Anopheles stephensi for potential malaria control
Authors: Liang Yongkang , Liu Julian , Wu YiLian , Wu Yu , Xi Zhiyong
Published: September 2024

The spread and invasion of the urban malaria vector Anopheles stephensi has emerged as a significant threat to ongoing malaria control and elimination efforts, particularly in Africa. The successful use of the maternally inherited endosymbiotic bacterium Wolbachia for arbovirus control has inspired the exploration of similar strategies for managing malaria vectors, necessitating the establishment of a stable Wolbachia-Anopheles symbiosis. In this study, we successfully transferred Wolbachia wPip into An. stephensi, resulting in the establishment of a stable transinfected HP1 line with 100% maternal transmission efficiency. We demonstrate that wPip in the HP1 line induces nearly complete unidirectional cytoplasmic incompatibility (CI) and maintains high densities in both somatic and germline tissues. Despite a modest reduction in lifespan and female reproductive capacity, our results suggest the Wolbachia infection in the HP1 line has little impact on life history traits, body size, and male mating competitiveness, as well as the ability of its larvae to tolerate rearing temperatures up to 38°C, although wPip densities moderately decrease when larvae are exposed to a constant 33°C and diurnal cyclic temperatures of 27–36°C and 27–38°C. These findings highlight the potential of the HP1 line as a robust candidate for further development in malaria control.
Ecological study measuring the association between conflict, environmental factors, and annual global cutaneous and mucocutaneous leishmaniasis incidence (2005–2022)
Authors: Tarnas Maia C. , Abbara Aula , Desai Angel N. , Parker Daniel M.
Published: September 2024

Background

Cutaneous and mucocutaneous leishmaniasis (CL/ML) cause significant morbidity globally and are vulnerable to changes from environmental events and conflict. In this ecological study, we aim to measure the associations between annual CL/ML cases, conflict intensity, and environmental factors between 2005 and 2022 globally.

Methods

We pulled annual case data from the WHO for 52 nations that had conflict intensity scores (ranging from 1–10) from the Bertelsmann Transformation Index. Using Earth observation tools, we gathered temperature, precipitation, vegetation, and humidity data, in addition to data on annual estimates of population, internal displacement, and GDP. We fit a negative binomial generalized additive model with a random nation-level intercept.

Results

Conflict was positively associated with increased CL/ML across the studied nations (IRR: 1.09, 95% CI: 1.01–1.16, p = 0.02). Given this, intense conflict (a score of ten) was associated with over double the risk of CL/ML compared to the lowest conflict levels (score of one). We also identified a curvilinear relationship between mean temperature and cases, as well as between vegetation level and cases. Each had small pockets of significant increased and decreased risk, respectively. Larger mean humidity ranges were negatively associated with cases. Importantly, the relationship between conflict intensity and cases was mediated by displacement.

Discussion

Conflict is significantly associated with increased CL/ML cases. This is especially true at higher conflict levels, marking when conflict turns violent. The destruction of critical infrastructure (e.g., that related to healthcare, water, and sanitation) often seen during conflict could drive this association. Such environments can be hospitable to sandflies and can heighten individuals’ vulnerability through increased malnutrition, poverty, and displacement. Understanding this relationship is crucial for public health preparedness and response, especially as conflicts become increasingly violent and protracted.
Serum-deprivation response of ARPE-19 cells; expression patterns relevant to age-related macular degeneration
Authors: Peterson Katherine M. , Mishra Sanghamitra , Asaki Esther , Powell John I. , He Yiwen , Berger Alan E. , Rajapakse Dinusha , Wistow Graeme
Published: September 2024

ARPE-19 cells are derived from adult human retinal pigment epithelium (RPE). The response of these cells to the stress of serum deprivation mimics some important processes relevant to age-related macular degeneration (AMD). Here we extend the characterization of this response using RNASeq and EGSEA gene set analysis of ARPE-19 cells over nine days of serum deprivation. This experiment confirmed the up-regulation of cholesterol and lipid-associated pathways that increase cholesterol levels in these cells. The gene expression analysis also identified other pathways relevant to AMD progression. There were significant changes in extracellular matrix gene expression, notably a switch from expression of collagen IV, a key component of Bruch’s membrane (part of the blood-retina barrier), to expression of a fibrosis-like collagen type I matrix. Changes in the expression profile of the extracellular matrix led to the discovery that amelotin is induced in AMD and is associated with the development of the calcium deposits seen in late-stage geographic atrophy. The transcriptional profiles of other pathways, including inflammation, complement, and coagulation, were also modified, consistent with immune response patterns seen in AMD. As previously noted, the cells resist apoptosis and autophagy but instead initiate a gene expression pattern characteristic of senescence, consistent with the maintenance of barrier function even as other aspects of RPE function are compromised. Other differentially regulated genes were identified that open new avenues for investigation. Our results suggest that ARPE-19 cells maintain significant stress responses characteristic of native RPE that are informative for AMD. As such, they provide a convenient system for discovery and for testing potential therapeutic interventions.
Is ChatGPT 3.5 smarter than Otolaryngology trainees? A comparison study of board style exam questions
Authors: Patel Jaimin , Robinson Peyton , Illing Elisa , Anthony Benjamin
Published: September 2024

Objectives

This study compares the performance of the artificial intelligence (AI) platform Chat Generative Pre-Trained Transformer (ChatGPT) to Otolaryngology trainees on board-style exam questions.

Methods

We administered a set of 30 Otolaryngology board-style questions to medical students (MS) and Otolaryngology residents (OR). 31 MSs and 17 ORs completed the questionnaire. The same test was administered to ChatGPT version 3.5, five times. Comparisons of performance were achieved using a one-way ANOVA with Tukey Post Hoc test, along with a regression analysis to explore the relationship between education level and performance.

Results

The average scores increased each year from MS1 to PGY5. A one-way ANOVA revealed that ChatGPT outperformed trainee years MS1, MS2, and MS3 (p = <0.001, 0.003, and 0.019, respectively). PGY4 and PGY5 otolaryngology residents outperformed ChatGPT (p = 0.033 and 0.002, respectively). For years MS4, PGY1, PGY2, and PGY3 there was no statistical difference between trainee scores and ChatGPT (p = .104, .996, and 1.000, respectively).

Conclusion

ChatGPT can outperform lower-level medical trainees on Otolaryngology board-style exam but still lacks the ability to outperform higher-level trainees. These questions primarily test rote memorization of medical facts; in contrast, the art of practicing medicine is predicated on the synthesis of complex presentations of disease and multilayered application of knowledge of the healing process. Given that upper-level trainees outperform ChatGPT, it is unlikely that ChatGPT, in its current form will provide significant clinical utility over an Otolaryngologist.
Bacterial diversity of cantaloupes and soil from Arizona and California commercial fields at the point of harvest
Authors: Goforth Madison , Obergh Victoria , Park Richard , Porchas Martin , Brierley Paul , Turni Tom , Patil Bhimanagouda , Ravishankar Sadhana , Huynh Steven , Parker Craig T. , Cooper Kerry K.
Published: September 2024

Across the United States, melons are a high demand crop reaching a net production of 2.7 million tons in 2020 with an economic value of $915 million dollars. The goal of this study was to characterize the bacterial diversity of cantaloupe rinds and soil from commercial melon fields at the point of harvest from two major production regions, Arizona, and California. Cantaloupes and composite soil samples were collected from three different commercial production fields, including Imperial Valley, CA, Central Valley, CA, and Yuma Valley, AZ, at the point of harvest over a three-month period, and 16S rRNA gene amplicon sequencing was used to assess bacterial diversity and community structure. The Shannon Diversity Index showed higher diversity among soil compared to the cantaloupe rind regardless of the sampling location. Regional diversity of soil differed significantly, whereas there was no difference in diversity on cantaloupe surfaces. Bray-Curtis Principal Coordinate Analysis (PCoA) dissimilarity distance matrix found the samples clustered by soil and melon individually, and then clustered tighter by region for the soil samples compared to the cantaloupe samples. Taxonomic analysis found total families among the regions to be 52 for the soil samples and 12 among cantaloupes from all three locations, but composition and abundance did vary between the three locations. Core microbiome analysis identified two taxa shared among soil and cantaloupe which were Bacillaceae and Micrococcaceae. This study lays the foundation for characterizing the cantaloupe microbiome at the point of harvest that provides the cantaloupe industry with those bacterial families that are potentially present entering post-harvest processing, which could assist in improving cantaloupe safety, shelf-life, cantaloupe quality and other critical aspects of cantaloupe post-harvest practices.
New antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing
Authors: Borges Kellen Christina Malheiros , Costa Vinícius Alexandre Fiaia , Neves Bruno , Kipnis André , Junqueira-Kipnis Ana Paula
Published: September 2024

Acinetobacter baumannii is a worldwide Gram-negative bacterium with a high resistance rate, responsible for a broad spectrum of hospital-acquired infections. A computational chemogenomics framework was applied to investigate the repurposing of approved drugs to target A. baumannii. This comprehensive approach involved compiling and preparing proteomic data, identifying homologous proteins in drug-target databases, evaluating the evolutionary conservation of targets, and conducting molecular docking studies and in vitro assays. Seven drugs were selected for experimental assays. Among them, tavaborole exhibited the most promising antimicrobial activity with a minimum inhibitory concentration (MIC) value of 2 μg/ml, potent activity against several clinically relevant strains, and robust efficacy against biofilms from multidrug-resistant strains at a concentration of 16 μg/ml. Molecular docking studies elucidated the binding modes of tavaborole in the editing and active domains of leucyl-tRNA synthetase, providing insights into its structural basis for antimicrobial activity. Tavaborole shows promise as an antimicrobial agent for combating A. baumannii infections and warrants further investigation in preclinical studies.
Prevalence and proportion by age and sex of chronic health conditions in a large healthcare system
Authors: Gronich Naomi , Saliba Walid , Schwartz Janice B.
Published: September 2024

Background

Disease prevalence and distribution by patient characteristics data are needed to guide “representative” patient enrollment in clinical trials and assess relevance of results to patient populations. Our objective was to describe disease prevalence, and age/sex distribution of patients with common chronic conditions from a large population sample.

Methods

A cross-sectional study of all members of Clalit Health Services, alive on January 1, 2020. Included were 26 chronic diseases, and 21 types of malignancies regarded as active by being diagnosed between January 1, 2018- to January 1, 2020, or by prescription of oncologic treatment medications January 1, 2018 and January 1, 2020.

Results

Data from 4,627,183 individuals, 2,274,349 males and 2,352,834 females from newborn to 110 years. Obesity (19%), hypertension (13%), diabetes mellitus (9%), esophagitis-gastritis (5.5%), thyroid disease (5.3%), asthma (5.1%), ischemic heart disease (4.5%), depression (4.5%), osteoporosis (3.8%), and atopic dermatitis (3.6%) were the ten most prevalent conditions. Proportions of age groups varied between conditions (67% of hypertensives were ≥65 years old, 24% ≥80 years; 73% with ischemic heart disease were ≥65 years, 29% ≥80 years; 59% of diabetics were ≥65 years, 17% ≥80 years; 42% of atrial fibrillation patients were ≥80 years; 40% of heart failure patients were ≥80 years). Proportions of males and females for most conditions paralleled prevalence except proportions of women increased after age 80 for cardiovascular diseases, and for diabetes after age 75. The five most frequent active cancers were breast, prostate, colon/rectal, lymphoma and melanoma. The prevalence of cancers increased with age beginning in the middle-aged groups and peaking at very old ages. Women had lower prevalence of lung cancers and accounted for lower percentages of patients with lung cancers (45 vs 55%) but similar percentages for women and men were seen in the patients with colon and rectal cancer (50.4 vs. 49.6% in women) and lymphoma (50.7 vs. 49.3% in women).

Conclusions

Prevalence of medical conditions and distributions differ by age and sex. This information serves as an example and resource for data needed to describe a “representative” clinical population.
Dimensional structure of the items from The Swedish Demand-Control-Support Questionnaire (DCSQ) used in The HUNT Study
Authors: Sperstad Jonil Tau , Coleman Grahame , Muri Karianne , Skjerve Eystein , Utaaker Kjersti Selstad , Torske Magnhild Oust
Published: September 2024

Objective

The Swedish Demand-Control-Support Questionnaire (DCSQ) is used to measure psychosocial work environment. Nine of the original 17 DCSQ items were used in the Trøndelag Health Study (HUNT) in 2017–2019 (HUNT4); three items from each of the three dimensions of demand, control, and support. The goal of this paper was to assess the internal reliability and dimensional structure of the nine DCSQ items used in HUNT4.

Method

HUNT4 participants registered with an occupation, and who had responded to all DCSQ items were included in the sample. Internal reliability and consistency of the nine DCSQ items were tested using composite reliability and item total correlation. A confirmatory factor analysis (CFA) was performed to determine whether the nine DCSQ items used in HUNT4 had a similar factor structure as the original 17 items. CFA was performed on the sample as a whole, before testing the models on different occupational groups to check if the dimensional structure remained the same.

Results

Of 56,041 HUNT4 participants (participation rate: 54%), 21,187 had a known occupation and responded to all nine DCSQ items. The mean age of the sample was 50.6 years (SD = 10.2), and the sample consisted of 57.3% females and 42.7% males. The best model fit was achieved by removing the item “Work creativity” (λ = 0.398, item total correlation 0.334) from the model. The same three-factorial structure as in the original DCSQ was seen with the remaining eight DCSQ items, with good internal consistency of all three dimensions (composite reliability ranged from 0.709 to 0.851). This dimensional structure remained the same when tested on all occupational groups.

Conclusion

The results indicate that the shortened version of the Swedish DCSQ used in HUNT4 can be used to assess aspects of demand, control, and social support at work.
Prediction of heavy metal ion distribution and Pb and Zn ion concentrations in the tailing pond area
Authors: Wu Pengfei , Chen Bowen , Li Runzhi , Li Ruochen
Published: September 2024

The pollution caused by tailings ponds has resulted in ecological damage, with soil contamination significantly impacting the daily lives of residents in the vicinity of mining areas and the future development of mining areas. This study assesses the transport status of heavy metal pollution in tailings areas and predicts its impact on future pollution levels. This study focused on lead–zinc tailing ponds, exploring the spatial and chemical distribution characteristics of heavy metals based on the distributions of Pb, Zn, As, Cu, Cr, Cd, Hg, and Ge ions. The concentrations of the major heavy metal ions Pb and Zn in tailings ponds were predicted via the exponential smoothing method. ① The total accumulation of Pb and Zn in the mine tailings ranges from 936.74~1212.61 mg/kg and 1611.85~2191.47 mg/kg, much greater than the total accumulation of the remaining six heavy metals. The total accumulation of associated heavy metal Cu was high, and the lowest total heavy metals were Hg and Ge at only 0.19 mg/kg and 1.05 mg/kg. ② The analyses of soil heavy metal chemical forms reveal that the heavy metals Pb and Zn had the highest exchangeable state content and state ratio and the strongest transport activity in the industrial plaza and village soils. Pb and Zn are the heavy metals with the greatest eco-environmental impacts in the mining area. ③ The predicted results show that the soil concentrations of the heavy metals Pb and Zn around the tailings area in 2026 are 1.335 and 1.191 times the predicted time starting values. The concentrations of the heavy metals Pb and Zn at the starting point of the forecast are already 3.34 and 3.02 times the upper limits of the environmental standard (according to environmental standards for gravelly grey calcium soils). These results have significant implications for heavy metal pollution risk management.
Distance interventions for enhancing preparedness in informal caregivers of older adults: A systematic review protocol
Authors: Dal Pizzol Fernanda L. F. , Hunter Kathleen F. , Baumbusch Jennifer , O’Rourke Hannah M.
Published: September 2024

Introduction

Informal caregivers provide care to older adults but report lack of preparedness to enact the role. Intervention programs delivered by distance offer one alternative to support preparedness. Three review studies conducted to date have highlighted the benefits of distance interventions for enhancing preparedness among informal caregivers of older adults. However, these reviews have been limited in presenting and discussing how intervention components influenced outcomes. Additionally, they have not compared different distance delivery approaches for informal caregivers of older adults or assessed their varying impact on preparedness outcomes. These limitations make the effectiveness of diverse distance approaches unclear.

Aim

To evaluate the effects of distance interventions aimed at enhancing preparedness among informal caregivers of older adults.

Methods

This protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines and is guided by the Cochrane Handbook for Systematic Reviews of Interventions. It has been registered in PROSPERO (CRD42023400668). Databases used in the search will include CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, Scopus, and ProQuest Theses and Dissertations Global. The search will not be restricted by publication year to include all relevant studies. Studies published in English and Portuguese will be included. Study quality will be assessed using Downs and Black’s checklist. If metanalysis is possible, it will be performed using the ReviewManager (RevMan) software.

Conclusions

The study will be the first of its type to systematically review and synthesize components and approaches of distance interventions aimed at supporting preparedness of informal caregivers of older adults.
Numerical study on the characteristics of viscous fingering during the displacement process of non-Newtonian fluid
Authors: Wu Yu-Ting , Qin Zhen , Ma Huaiyu , Lyu Sung-Ki
Published: September 2024

This study uses numerical methods (ANSYS-Fluent) to investigate the viscous fingering of the displaced phase as a shear-thinning fluid in the classic three-dimensional Hele-Shaw cell. Comparing the behavior of fingerings with different properties on the upper and lower surfaces of a three-dimensional model, it was found that when the upper and lower surfaces are walls, under the combined action of moving contact lines and Saffman-Taylor instability, fingering splitting occurs at the tip, resulting in the appearance of two fingers at the interface. In addition, we have found that interfacial tension has a suppressive effect on short waves. As the interfacial tension increases, the velocity at the advancing tip decreases. Therefore, when the interface tension is 0, viscous fingering displacement reaches the farthest distance. We have also conducted research on the viscous fingering at different temperatures. The results indicate that increasing the temperature leads to a decrease in the viscosity of the displaced phase, making the flow more stable. As the temperature rises, the pressure gradient inside the flow path increases, pushing the viscous fingering further.
Aβ25-35-induced autophagy and apoptosis are prevented by the CRMP2-derived peptide ST2-104 (R9-CBD3) via a CaMKKβ/AMPK/mTOR signaling hub
Authors: Ji Yingshi , Ren Jinghong , Qian Yuan , Li Jiaxin , Liu Huanyu , Yao Yuan , Sun Jianfeng , Khanna Rajesh , Sun Li
Published: September 2024

We previously reported that the peptide ST2-104 (CBD3, for Ca2+ channel-binding domain 3), derived from the collapsin response mediator protein 2 (CRMP2)–a cytosolic phosphoprotein, protects neuroblastoma cells against β-amyloid (Aβ) peptide-mediated toxicity through engagement of a phosphorylated CRMP2/NMDAR pathway. Abnormal aggregation of Aβ peptides (e.g., Aβ25–35) leads to programmed cell death (apoptosis) as well autophagy–both of which contribute to Alzheimer’s disease (AD) progression. Here, we asked if ST2-104 affects apoptosis and autophagy in SH-SY5Y neuroblastoma challenged with the toxic Aβ25–35 peptide and subsequently mapped the downstream signaling pathways involved. ST2-104 protected SH-SY5Y cells from death following Aβ25–35 peptide challenge by reducing apoptosis and autophagy as well as limiting excessive calcium entry. Cytotoxicity of SHY-SY5Y cells challenged with Aβ25–35 peptide was blunted by ST2-104. The autophagy activator Rapamycin blunted the anti-apoptotic activity of ST2-104. ST2-104 reversed Aβ25-35-induced apoptosis via inhibiting Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ)-mediated autophagy, which was partly enhanced by STO-609 (an inhibitor of CaMKKβ). ST2-104 attenuated neuronal apoptosis by inhibiting autophagy through a CaMKKβ/AMPK/mTOR signaling hub. These findings identify a mechanism whereby, in the face of Aβ25–35, the concerted actions of ST2-104 leads to a reduction in intracellular calcium overload and inhibition of the CaMKKβ/AMPK/mTOR pathway resulting in attenuation of autophagy and cellular apoptosis. These findings define a mechanistic framework for how ST2-104 transduces “outside” (calcium channels) to “inside” signaling (CaMKKβ/AMPK/mTOR) to confer neuroprotection in AD.
Development of knowledge, attitude and practice questionnaires on e-Huffaz ProHealth, a multicomponent lifestyle intervention module among Tahfiz students
Authors: Che Wan Mohd Rozali Wan Nor Atikah , Ishak Ismarulyusda , Mat Ludin Arimi Fitri , Mad Azli Amanina Athirah , Solah Nurul ‘Izzah , Ibrahim Farah Wahida , Abd Warif Nor Malia
Published: September 2024

e-Huffaz ProHealth is a lifestyle intervention module developed specifically for Tahfiz students. The e-Huffaz ProHealth consists of physical health, nutritional and psychological components. This study aimed to develop the knowledge, attitude and practice (KAP) questionnaires on e-Huffaz ProHealth among Tahfiz students. This cross-sectional pilot study was conducted in 2022. The first phase entailed developing the KAP questionnaires. The second phase involved determining the content validity and face validity. While the third phase involved evaluating the reliability. A total of six experts from public academic institutions participated in the initial evaluation stage to assess validity while five experts were involved in the second stage. Thirty-three and 41 respondents were involved for the face validity and reliability evaluation, respectively. The questionnaires were distributed via Google Docs and hard copies were handed out in person to Tahfiz school teachers and students at Madrasah Tahfiz Al-Amani and Pondok Moden Tahfiz Saadah Addaarain. The findings demonstrated that the Item Content Validity Index (I-CVI) for the three components of the KAP questionnaires at the second stage of evaluation was high (1.0). The scores for the Scale Face Validity Average Index (S-FVI/Average) in assessing the level of clarity and understanding for the three components were 0.89 and 0.88, 0.92 and 0.90, and 0.88 and 0.9, respectively. Meanwhile, the reliability of KAP for physical activity was moderate (0.43), very high (0.91) and high (0.7), respectively. For nutrition, the reliability of KAP was good and acceptable with the values of 0.63, 0.83 and 0.65, respectively. The results of reliability of KAP for psychological well-being was good with the values of 0.54, 0.56 and 0.84, respectively. The KAP questionnaires of e-Huffaz ProHealth was successfully developed with high content validity, good face validity and acceptable reliability. Hence, it can be used for future study to evaluate the effectiveness of e-Huffaz ProHealth among Tahfiz students.
A novel viral RNA detection method based on the combined use of trans-acting ribozymes and HCR-FRET analyses
Authors: Ferreira da Silva Leonardo , Valle Garay Aisel , Queiroz Pedro Felipe , Garcia de Resende Sophia , Gomide Mayna , Moreira de Oliveira Izadora Cristina , Souza Bernasol Amanda , Arce Anibal , Canet Santos Liem , Torres Fernando , Silva-Pereira Ildinete , de Freitas Sonia Maria , Marques Coelho Cíntia
Published: September 2024

The diagnoses of retroviruses are essential for controlling the rapid spread of pandemics. However, the real-time Reverse Transcriptase quantitative Polymerase Chain Reaction (RT-qPCR), which has been the gold standard for identifying viruses such as SARS-CoV-2 in the early stages of infection, is associated with high costs and logistical challenges. To innovate in viral RNA detection a novel molecular approach for detecting SARS-CoV-2 viral RNA, as a proof of concept, was developed. This method combines specific viral gene analysis, trans-acting ribozymes, and Fluorescence Resonance Energy Transfer (FRET)-based hybridization of fluorescent DNA hairpins. In this molecular mechanism, SARS-CoV-2 RNA is specifically recognized and cleaved by ribozymes, releasing an initiator fragment that triggers a hybridization chain reaction (HCR) with DNA hairpins containing fluorophores, leading to a FRET process. A consensus SARS-CoV-2 RNA target sequence was identified, and specific ribozymes were designed and transcribed in vitro to cleave the viral RNA into fragments. DNA hairpins labeled with Cy3/Cy5 fluorophores were then designed and synthesized for HCR-FRET assays targeting the RNA fragment sequences resulting from ribozyme cleavage. The results demonstrated that two of the three designed ribozymes effectively cleaved the target RNA within 10 minutes. Additionally, DNA hairpins labeled with Cy3/Cy5 pairs efficiently detected target RNA specifically and triggered detectable HCR-FRET reactions. This method is versatile and can be adapted for use with other viruses. Furthermore, the design and construction of a DIY photo-fluorometer prototype enabled us to explore the development of a simple and cost-effective point-of-care detection method based on digital image analysis.
Negative prognostic impact of tumor deposits in stage III colorectal cancer patients
Authors: Ma Ting , Qin Zhaofu , Xu Guohui , Zheng Peng-Wen , Feng Longhai , Ma Dening , Fu Zhixuan , Gao Xinyi
Published: September 2024

Background

The prognostic value of tumor deposits (TDs) in stage III colorectal cancer (CRC) patients is poorly described based on the current tumor node metastasis (TNM) stage system.

Materials and methods

Based on the data from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 to 2020 and local hospital between 2006 to 2022, the clinicopathological features of stage III CRC patients with TDs were screened by Chi-square test. Kaplan-Meier curves were performed to describe the significant difference in overall survival (OS) among the different groups, and log-rank tests were used to compare the cumulative survival distributions.

Result

Patients with TDs exhibited more aggressive tumors, characterized by advanced T staging (T3&T4), N staging (N2), perineural invasion, and more advanced TNM stage. The presence of TDs was identified as a negative prognostic factor in stage III CRC patients, with the co-existence of TDs and lymph node metastasis associated the poorest prognosis. A pairwise comparison revealed no statistically significant difference between TD+N1a/b and N1c groups, while the OS of TD-LN+ (TD- N1a/b) patients was the most favorable within the N1 stage. Notably, patients with a single lymph node positive had a significantly better OS than those with a single TD positive.

Conclusion

The presence of tumor deposits was a negative prognostic factor in stage III colorectal cancer patients, and the significance of tumor deposits was underestimated in the current TNM staging system.
The association between mode of childbirth delivery and early childhood caries: A comprehensive systematic review and meta-analysis
Authors: Xiang Li , Kozlitina Iuliia A. , Mohammadian Mahdi , Choopani Roya , Mohammadian-Hafshejani Abdollah
Published: September 2024

Background

Early childhood caries (ECC), also known as dental caries, poses a significant challenge to the oral health and overall well-being of young children. This study aims to investigate the potential relationship between the mode of delivery and the odds of ECC.

Methods

We conducted a meticulous systematic review and meta-analysis, gathering studies from reputable databases, including Web of Science, Scopus, PubMed, Cochrane, Google Scholar, and Embase. The selected studies underwent rigorous evaluation for heterogeneity, utilizing statistical tests such as the Chi-square test, I2, meta-regression analysis, sensitivity analysis, and subgroup analysis. We assessed the presence of publication bias using Begg’s and Egger’s tests, while the quality of the articles was evaluated using the Newcastle-Ottawa Scale checklist.

Results

Our analysis included a robust dataset of 24 studies conducted between 1997 and 2024, involving a total of 71,732 participants. The meta-analysis revealed an odds ratio of 1.05 (95% CI: 0.86–1.30; P-value = 0.610) for dental caries in children born via cesarean section. Importantly, we found no evidence of publication bias, as indicated by non-significant results from Begg’s test (P-value = 0.568) and Egger’s test (P-value = 0.807). Meta-regression analysis did not identify any significant associations between the study variables and the observed heterogeneity (P > 0.10). Sensitivity analysis further confirmed the stability of the study results, with no significant changes detected.

Conclusion

In conclusion, our comprehensive meta-analysis provides compelling evidence that there is no significant association between the mode of delivery and the odds of ECC. These findings enhance our understanding of this important topic and have implications for clinical practice and public health interventions.
PrEP discontinuation, cycling, and risk: Understanding the dynamic nature of PrEP use among female sex workers in South Africa
Authors: Shipp Lillian M. , Ryan Sofia , Comins Carly A. , Mcingana Mfezi , Mulumba Ntambue , Guddera Vijayanand , Phetlhu Deliwe Rene , Hausler Harry , Baral Stefan D. , Schwartz Sheree R.
Published: September 2024

PrEP cycling among women is thought to be safe when there are distinct “seasons of risk.” However, cyclical PrEP use over short periods may be associated with increased risk of HIV acquisition. We aimed to characterize key social ecological factors contributing toward PrEP cycling among female sex workers (FSW) in the context of high HIV risk. Semi-structured, in-depth interviews were conducted with 36 FSW at risk for HIV acquisition and 12 key informant (KI) service providers in eThekwini (Durban), South Africa from January-October 2020. FSW identified key factors driving temporary discontinuation of PrEP including relocation, lack of information on or difficulty coping with side effects, and delays in accessing PrEP. In many cases, FSW were motivated to restart PrEP once barriers were overcome. In contrast, KIs emphasized the importance of individual adherence to PrEP and reliance on personal risk assessments when counselling FSW on cycling decisions. FSW and KI perspectives highlight a disconnect between providers’ recommendations on the potential for cyclical use of PrEP during periods of minimal risk and actual drivers among FSW causing temporary PrEP discontinuation. Further interventions supporting safe PrEP cycling are needed to ensure decisions around cycling are deliberate and guided by changes in HIV risk rather than external factors.
Advancing one health vaccination: In silico design and evaluation of a multi-epitope subunit vaccine against Nipah virus for cross-species immunization using immunoinformatics and molecular modeling
Authors: Banico Edward Coralde , Sira Ella Mae Joy Sinco , Fajardo Lauren Emily , Dulay Albert Neil Gura , Odchimar Nyzar Mabeth Obenio , Simbulan Alea Maurice , Orosco Fredmoore Legaspi
Published: September 2024

The resurgence of the Nipah virus (NiV) in 2023 has raised concerns for another potentially severe pandemic, given its history of high mortality from previous outbreaks. Unfortunately, no therapeutics and vaccines have been available for the virus. This study used immunoinformatics and molecular modeling to design and evaluate a multi-epitope subunit vaccine targeting NiV. The designed vaccine construct aims to stimulate immune responses in humans and two other intermediate animal hosts of the virus—swine and equine. Using several epitope prediction tools, ten peptides that induced B-lymphocyte responses, 17 peptides that induced cytotoxic T-lymphocyte (CTL) responses, and 12 peptides that induced helper T-lymphocyte (HTL) responses were mapped from nine NiV protein sequences. However, the CTL and HTL-inducing peptides were reduced to ten and eight, respectively, following molecular docking and dynamics. These screened peptides exhibited stability with 30 common major histocompatibility complex (MHC) receptors found in humans, swine, and equine. All peptides were linked using peptide linkers to form the multi-epitope construct and various adjuvants were tested to enhance its immunogenicity. The vaccine construct with resuscitation-promoting factor E (RpfE) adjuvant was selected as the final design based on its favorable physicochemical properties and superior immune response profile. Molecular docking was used to visualize the interaction of the vaccine to toll-like receptor 4 (TLR4), while molecular dynamics confirmed the structural stability of this interaction. Physicochemical property evaluation and computational simulations showed that the designed vaccine construct exhibited favorable properties and elicited higher antibody titers than the six multi-epitope NiV vaccine designs available in the literature. Further in vivo and in vitro experiments are necessary to validate the immunogenicity conferred by the designed vaccine construct and its epitope components. This study demonstrates the capability of computational methodologies in rational vaccine design and highlights the potential of cross-species vaccination strategies for mitigating potential NiV threats.
Understanding the unmet support needs of young and young adult carers and their families
Authors: Brimblecombe Nicola , Stevens Madeleine , Gowen Sara , Skyer Robin , Moriarty Jo
Published: September 2024

Support for children and young people who provide unpaid care is important to help prevent negative impacts of caregiving on their education, employment, mental health, and social relationships. We aimed to address an evidence gap about what services and support are needed from young carers’ perspectives. We carried out focus groups or in-depth interviews with 133 carers aged 9–25 in England. Expressed unmet need for services and support could be grouped in three categories: support that would reduce or remove young people’s need to provide care, help improve the lives of the people they care for, mitigate against impacts of providing care on their mental health, wellbeing, education, social participation and leisure activities, and, whilst they are still providing care, assist them in their caring role. Action is needed to address these currently unmet needs and implement young carers’ and their families’ rights to support.
The experiences of hospital staff with decision-making concerning patient enrolment in hospital at home services: A complex and dynamic process
Authors: Karlsen Lillian , Mjølstad Bente Prytz , Løfaldli Bjarte Bye , Helvik Anne-Sofie
Published: September 2024

Background

Hospital at home care services offer a potential solution to the problem of strain on hospital beds while simultaneously enhancing patient outcomes. Nevertheless, implementation of the hospital at home care model is associated with several challenges. One such barrier involves patient enrolment, particularly during the initial stage of service operation. Due to their frontline experience, healthcare professionals possess valuable insights that can help us understand and address this challenge. This study aimed to explore the experiences of hospital staff in the decision-making process concerning patient enrolment in hospital at home.

Methods

In total, 22 semi-structured individual interviews were conducted with hospital staff members between January and May 2022 at the participants’ workplace or in a public office depending on their preferences. Data were analysed using reflexive thematic analysis.

Results

We identified four themes pertaining to the experiences of hospital staff with the decision-making process concerning patient enrolment in hospital at home: “beneficial for the patients; an important motivating factor”, “patient eligibility; prioritizing safety”, “contextual factors within hospital ward units; opportunities and limitations”, and “collaboration with municipalities; crucial but challenging”.

Conclusions

Hospital staff described a complex and dynamic decision-making process when considering patient eligibility for enrolment to hospital at home services. The findings highlight both barriers and enablers pertaining to this process and emphasize the need to provide support to hospital staff as they navigate this complex situation. A key finding pertains to the critical importance of high-quality decision-making in ensuring positive outcomes and the overall effectiveness of hospital at home care services. Additionally, this study proposes a deeper exploration of the ethical considerations associated with balancing the goal of patient safety with that of equitable access to high-quality, person-centred care within the context of hospital at home.
The heat shock protein 90 inhibitor RGRN-305 attenuates SARS-CoV-2 spike protein-induced inflammation in vitro but lacks effectiveness as COVID-19 treatment in mice
Authors: Ben Abdallah Hakim , Marino Giorgia , Idorn Manja , S. Reinert Line , Bregnhøj Anne , Paludan Søren Riis , Johansen Claus
Published: September 2024

The inhibition of heat shock protein 90 (HSP90), a molecular chaperone, has been proposed to be a potential novel treatment strategy for Coronavirus disease 2019 (COVID-19). In contrast to other studies, our data demonstrated that RGRN-305, a HSP90 inhibitor, exacerbated the cytopathic effect and did not reduce the viral shedding in VeroE6-hTMPRSS2 cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Likewise in a murine model of SARS-CoV-2, transgenic mice treated orally with RGRN-305 exhibited reduced survival by the end of the experiment (day 12) as 14% (1/7) survived compared to 63% (5/8) of those treated with drug-vehicle. Animal weight was not reduced by the RGRN-305 treatment. Interestingly, we demonstrated that inhibition of HSP90 by RGRN-305 significantly dampened the inflammatory response induced by SARS-CoV-2 spike protein in human macrophage-like cells (U937) and human lung epithelial cells (A549). Measured by quantitative real-time PCR, the mRNA expression of the proinflammatory cytokines TNF, IL1B and IL6 were significantly reduced. Together, these data suggest that HSP90 inhibition by RGRN-305 exacerbates the SARS-CoV-2 infection in vitro and reduces the survival of mice infected with SARS-CoV-2, but exhibits strong anti-inflammatory properties. This data shows that while RGRN-305 may be helpful in a ‘cytokine storm’, it has no beneficial impact on viral replication or survival in animals as a monotherapy. Further animal studies with HSP90 inhibitors in combination with an anti-viral drug may provide additional insights into its utility in viral infections and whether HSP90 inhibition may continue to be a potential treatment strategy for COVID-19 disease.