bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploratory Study on COPD Phenotypes and their Progression: Integrating SPECT and qCT Imaging Analysis
Authors: Li Frank , Zhang Xuan , Comellas Alejandro P. , Hoffman Eric A. , Graham Michael M. , Lin Ching-Long
Published: April 2024

Background

The objective of this study is to understand chronic obstructive pulmonary disease (COPD) phenotypes and their progressions by quantifying heterogeneities of lung ventilation from the single photon emission computed tomography (SPECT) images and establishing associations with the quantitative computed tomography (qCT) imaging-based clusters and variables.

Methods

Eight COPD patients completed a longitudinal study of three visits with intervals of about a year. CT scans of these subjects at residual volume, functional residual capacity, and total lung capacity were taken for all visits. The functional and structural qCT-based variables were derived, and the subjects were classified into the qCT-based clusters. In addition, the SPECT variables were derived to quantify the heterogeneity of lung ventilation. The correlations between the key qCT-based variables and SPECT-based variables were examined.

Results

The SPECT-based coefficient of variation (CVTotal), a measure of ventilation heterogeneity, showed strong correlations (|r| ≥ 0.7) with the qCT-based functional small airway disease percentage (fSAD%Total) and emphysematous tissue percentage (Emph%Total) in the total lung on cross-sectional data. As for the two-year changes, the SPECT-based maximum tracer concentration (TCmax), a measure of hot spots, exhibited strong negative correlations with fSAD%Total, Emph%Total, average airway diameter in the left upper lobe, and airflow distribution in the middle and lower lobes.

Conclusion

Small airway disease is highly associated with the heterogeneity of ventilation in COPD lungs. TCmaxis a more sensitive functional biomarker for COPD progression than CVTotal. Besides fSAD%Totaland Emph%Total, segmental airways narrowing and imbalanced ventilation between upper and lower lobes may contribute to the development of hot spots over time.
Impact of COVID-19 on diabetes mellitus outcomes and care in sub-Saharan Africa: A scoping review
Authors: Sseguya Wenceslaus , Bahendeka Silver , MacLennan Sara , Mody Nimesh , Guntupalli Aravinda Meera
Published: April 2024

Background

The COVID-19 pandemic impacted diabetes mellitus clinical outcomes and chronic care globally. However, little is known about its impact in low-resource settings such as sub-Saharan Africa. Hence, to address this, we systematically conducted a scoping review to explore the COVID-19 impact on diabetes outcomes and care in countries of sub-Saharan Africa.

Methods

We applied our search strategy to PubMed, Web of Science, CINAHL, African Index Medicus, Google Scholar, Cochrane Library, Scopus, Science Direct, ERIC and Embase to obtain relevant articles published from January 2020 to March 2023. Two independent reviewers were involved in the screening of retrieved articles. Data from eligible articles were extracted from quantitative, qualitative and mixed methods studies. Numerical data were summarised using descriptive statistics, while a thematic framework was used to categorise and identify themes for qualitative data.

Results

We found 42 of the retrieved 360 articles eligible, mainly from South Africa, Ethiopia and Ghana (73.4%). COVID-19 increased the risk of death (OR 1.30 – 9.0, 95% CI), hospitalisation (OR 3.30 – 3.73: 95% CI), and severity (OR: 1.30-4.05, 95% CI) in persons with diabetes mellitus. COVID-19 also increased the risk of developing diabetes mellitus in hospitalised cases. The pandemic, on the other hand, was associated with disruptions in patient self-management routine and diabetes mellitus care service delivery. Three major themes emerged, namely, (i) patient-related health management challenges, (ii) diabetes mellitus care service delivery challenges, and (iii) reorganisation of diabetes mellitus care delivery.

Conclusion

COVID-19 increased mortality and morbidity among people living with diabetes mellitus. In addition, the COVID-19 pandemic worsened diabetes mellitus care management. Sub-Saharan African countries should, therefore, institute appropriate policy considerations for persons with diabetes mellitus during widespread emergencies.
Modeling the interplay between disease spread, behaviors, and disease perception with a data-driven approach
Authors: De Gaetano Alessandro , Barrat Alain , Paolotti Daniela
Published: April 2024

Individuals’ perceptions of disease influence their adherence to preventive measures, shaping the dynamics of disease spread. Despite extensive research on the interaction between disease spread, human behaviors, and interventions, few models have incorporated real-world behavioral data on disease perception, limiting their applicability. This study novelly integrates disease perception, represented by perceived severity, as a critical determinant of behavioral change into a data-driven compartmental model to assess its impact on disease spread. Using survey data, we explore scenarios involving a competition between a COVID-19 wave and a vaccination campaign, where individuals’ behaviors vary based on their perceived severity of the disease. Results demonstrate that behavioral heterogeneities influenced by perceived severity affect epidemic dynamics, with high heterogeneity yielding contrasting effects. Longer adherence to protective measures by groups with high perceived severity provides greater protection to vulnerable individuals, while premature relaxation of behaviors by low perceived severity groups facilitates virus spread. Epidemiological curves reveal that differences in behavior among groups can eliminate a second infection peak, resulting in a higher first peak and overall more severe outcomes. The specific modeling approach for how perceived severity modulates behavior parameters does not strongly impact the model’s outcomes. Sensitivity analyses confirm the robustness of our findings, emphasizing the consistent impact of behavioral heterogeneities across various scenarios. Our study underscores the importance of integrating risk perception into infectious disease transmission models and highlights the necessity of extensive data collection to enhance model accuracy and relevance.
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 ASG , Ahmed Tahmeed , Jubayer Shamim , Kelman Ilan
Published: April 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.
Enabling a Learning Public Health System: Enhanced Surveillance of HIV and Other Sexually Transmitted Infections
Authors: Nieva Harry Reyes , Zucker Jason , Tucker Emma , Castor Delivette , Yin Michael T. , Gordon Peter , Elhadad Noémie
Published: April 2024

Sexually transmitted infections (STIs) continue to pose a substantial public health challenge in the United States (US). Surveillance, a cornerstone of disease control and prevention, can be strengthened to promote more timely, efficient, and equitable practices by incorporating health information exchange (HIE) and other large-scale health data sources into reporting. New York City patient-level electronic health record data between January 1, 2018 and June 30, 2023 were obtained from Healthix, the largest US public HIE. Healthix data were linked to neighborhood-level information from the American Community Survey. In this cross-sectional study, we compared patients who received a test or tested positive for chlamydia, gonorrhea, and/or HIV with patients who were untested or tested negative, respectively, using generalized estimating equations with logit function and robust standard errors. Among 1,519,121 tests performed for chlamydia, 1,574,772 for gonorrhea, and 1,200,560 for HIV, 2%, 0.6% and 0.3% were positive for chlamydia, gonorrhea, and HIV, respectively. Chlamydia and gonorrhea co-occurred in 1,854 cases (7% of chlamydia and 21% of gonorrhea total cases). Testing behavior was often incongruent with geographic and sociodemographic patterns of positive cases. For example, people living in areas with the highest levels of poverty were less likely to test for gonorrhea but almost twice as likely to test positive compared to those in low poverty areas. Regional HIE enabled review of testing and cases using granular and complementary data not typically available given existing reporting practices. Enhanced surveillance spotlights potential incongruencies between testing patterns and STI risk in certain populations, signaling potential under- and over-testing. These and future insights derived from HIE data may be used to continuously inform public health practice and drive further improvements in provision and evaluation of services and programs.
Trend of new cases of Human Immunodeficiency Virus infections in two health facilities in the Northern Cameroon between 2021-2022
Authors: Djataou Patrice , Djuidje Marceline Ngounoue , Nguefack-Tsague Georges , de Dieu Anoubissi Jean , Kameni Joel Kadji , Tiga Aline , Elong Elise , Djaouda Moussa , Ndjolo Alexis , Nkenfou Céline Nguefeu
Published: April 2024

HIV/AIDS continues to be a global public health problem. Studies of the incidence and prevalence of HIV and other sexually transmitted infections (STIs) that may contribute to or aggravate its acquisition remain an effective means of prevention. In recent years, terrorist groups have established themselves in the northern regions of Cameroon. This insecurity has led to a large influx of refugees with no information about their HIV and STI status. Given this above mentioned situation, this study aimed to assess the incidence and prevalence of HIV and STI and their associated risk factors in order to adjust strategies to monitor the epidemic. A cohort of 684 consenting participants from the North and Far North were enrolled in the study in 2021 and followed up in 2022 to measure the incidence and prevalence of HIV and to assess some associated risk factors. Each participant was administered a pretested questionnaire to collect sociodemographic variables and risk behaviors. Anti-HIV Ab, HBsAg (Hepatitis B Surface Antigen), TPHA (Treponema PallidumHemagglutination Assay) tests were performed. The data were compiled using EPI Info 7.5.2 for epidemiological analyses. The association between co-infections of HIV, Hepatitis, and syphilis and HIV incidence was evaluated using the Chi-2 test. The HIV incidence and overall prevalence were 1.63% (163/10,000 population) and 3.8%, respectively. The HIV incidence increased from 0.27% in 2017 (DHS) to 1.63% in the North and Far North regions as found in our study. The incidences of syphilis and hepatitis B were 1.03% and 4.56%, respectively. Factors associated with HIV acquisition included religion (Muslims being more infected, P<0.03), unprotected sex with a new partner (P<0.007), having a sex worker as a partner (P<0.0001), and co-infection with syphilis and hepatitis B (P<0.05). The findings also link increased HIV incidence to insecurity and population displacement. In HIV prevention strategies, it is important to consider the security and political stability context as well as HIV-associated infections such as hepatitis B and syphilis.
Identification of ovarian high-grade endometrioid-type tumors through multi-omics analysis: JGOG3025-TR2 study
Authors: Takamatsu Shiro , Hillman R. Tyler , Yoshihara Kosuke , Baba Tsukasa , Shimada Muneaki , Yoshida Hiroshi , Kajiyama Hiroaki , Oda Katsutoshi , Mandai Masaki , Okamoto Aikou , Enomoto Takayuki , Matsumura Noriomi
Published: April 2024

Objective

There is considerable interobserver variability in the differential diagnosis between ovarian high-grade endometrioid carcinoma (HGEC) and ovarian high-grade serous carcinoma (HGSC) due to their histopathological similarities. While the association between homologous recombination deficiency (HRD) and platinum sensitivity and PARP inhibitors is well established in HGSC, the molecular characteristics of HGEC remain unclear.

Methods

Fresh-frozen tissue samples from 15 ovarian HGECs and 274 ovarian HGSCs morphologically diagnosed by central pathology review in the Japanese Gynecological Oncology Group (JGOG) were subjected to targeted DNA sequencing, RNA sequencing, DNA methylation array, and SNP array analysis. Tumors were classified by unsupervised clustering based on copy number variation signatures. External datasets including 555 ovarian HGSCs and 287 endometrial high-grade carcinomas from The Cancer Genome Atlas project (TCGA-OV and TCGA-UCEC) were also analyzed.

Results

Four distinct groups were identified in the JGOG cohort. C1 (n=41) showedCCNE1amplification and poor survival. C2 (n=160) and C3 (n=59) showed a high frequency ofBRCAalterations with moderate and low aneuploidy, respectively. C4 (n=22) was characterized by favorable survival, higher frequency of HGEC, absence of bothBRCAalteration andCCNE1amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, andWT1gene expression. Additionally, C4 exhibited a normal endometrium-like DNA methylation profile and was defined as an “HGEC-type” tumor. The HGEC-type tumors were also identified in TCGA-OV and TCGA-UCEC.

Conclusions

Ovarian HGEC-type tumors exhibit non-HRD status, a favorable prognosis, and endometrial differentiation, and may comprise a subset of tumors diagnosed as HGSC.
The Spectrum from Overt Primary Aldosteronism to Mild Dysregulated Aldosterone Production in Incidentally Discovered Adrenocortical Adenomas
Authors: Uslar Thomas , Olmos Roberto , Burnier Alberth , Sanfuentes Benjamín , Böhm Pauline , Orellana Maria Paz , Guarda Francisco J. , Huete Álvaro , Mertens Nicolás , Besa Cecilia , Andía Marcelo , Majerson Alejandro , Cartes Jaime , Fardella Carlos , Allende Fidel , Solari Sandra , Vaidya Anand , Baudrand Rene
Published: April 2024

Background

Incidental adrenocortical adenomas (IA) are common. Current guidelines suggest screening for primary aldosteronism (PA) only in cases of hypertension or hypokalemia. This study aimed to evaluate the spectrum from overt PA to mild dysregulated aldosterone production with a sensitive protocol irrespective of blood pressure (BP) and potassium in patients with IA.

Methods

254 consecutive patients (excluding hypercortisolism) were evaluated. The spectrum of PA was defined as a suppressed renin plus the following criteria: 1)Overt PA: aldosterone-to-renin-ratio (ARR) >30 ng/dL-to-ng/mL/hr, plasma aldosterone concentration (PAC) >15ng/dL, and/or 24h urinary aldosterone >10 ug/24h; 2)Moderate PA: ARR 20-30 ng/dL-to-ng/mL/hr, PAC 10-15 ng/dL; 3)Mild dysregulated aldosterone production: ARR <20 ng/dL-to-ng/mL/hr and PAC >5-10 ng/dL.

Results

35% (n=89/254) met criteria for PA spectrum, 20% (34/89) were initially normotensive and 94% (84/89) normokalemic. Overt, moderate, and mild groups were 10%, 12%, and 13%. There were trends across groups of clinical severity: systolic BP (153±19, 140±14, 137±14 mmHg, p-trend<0.05), resistant hypertension (50%, 23%, 7% p-trend=<0.001), daily defined dose of antihypertensives (DDD) (3.2±1.6, 1.2±1.5, 0.4±0.6 p-trend=0.001), and lower eGFR (75.5±30.8, 97.8±38.5, 101±25.5, p-trend<0.01). At follow-up (mean 28±15 months), 87% had treatment with MR antagonists or surgery with decreased systolic BP relative to clinical severity, −31.3 ±23, −12.7 ±19, and −11.4 ±19 mmHg, (p-trend<0.001). Similar trends were observed for DDD, with significant increase in renin.

Conclusions

There is a prevalent spectrum of clinically-relevant PA and dysregulated aldosterone production in IA, irrespective of BP or potassium, usually undetected. Aldosterone-directed treatment improved BP and normalized renin even in milder cases.

GRAPHIC ABSTRACT
Efficacy of a physical activity regimen on visual outcomes among persons newly diagnosed with abnormal glucose tolerance: Study protocol for a pilot randomized controlled trial
Authors: Antiri Ebenezer Oduro , Hormenu Thomas , Ansah Edward Wilson , Ocansey Stephen , Arthur Rudolf Aaron , Awlime-Ableh Eric , Salifu Iddrisu , Nyane Benjamin , Gabla Augustine Mac-Hubert , Paku Juliet Elikem
Published: April 2024

Background: Abnormal Glucose Tolerance (AGT), which encompasses diabetes and prediabetes, is a growing health problem globally. It is affecting millions and predisposing such patients to several complications, including ocular complications. Physical activity has been found to improve glycemic levels, but the specific effect on visual outcomes in a newly diagnosed African population with AGT is yet to be explored fully. This pilot randomized controlled trial seeks to evaluate the efficacy of a physical activity intervention among newly diagnosed persons with AGT in Cape Coast, Ghana.

Methods: An ostensibly healthy population will be screened for AGT. Persons newly diagnosed with AGT will be recruited into the randomized controlled trial. About 50 newly diagnosed participants with AGT will undergo a 12-week moderate-to-vigorous physical activity (MVPA) intervention, specifically exercises that burn more than 3.0 metabolic equivalents (METs), to ascertain its effect on their visual acuity, contrast sensitivity, central visual field and diabetic retinopathy status. The participants will be randomized into a physical activity intervention group and a control group. Assessments will be done at baseline, and treatment outcomes will be done on the last day of the intervention for each participant.

Discussion: Physical activity is a proven lifestyle intervention that reduces glycemic levels in people with AGT. Unfortunately, many persons are unaware of their high level of glucose tolerance, which is associated with the deterioration of vision. This study intends to investigate and present findings on the advantages of physical activity interventions on visual outcomes among people with AGT. The study holds promise in informing evidence-based interventions for persons with AGT in poor economies.
Recovery and discharge time between remimazolam tosylate and propofol in hysteroscopy anesthesia: a randomized controlled study
Authors: Lin Xiangyi , Chen Shengjie , Liang Huiyan
Published: April 2024

Background

Hysteroscopy is considered the gold standard for the evaluation and treatment of uterine and endometrial lesions, but the operation is accompanied by severe pain, so it needs to be performed under anesthesia. Currently, a new sedative drug, remimazolam tosilate, can be used in digestive endoscopy and bronchoscopy. We will study its effect on hysteroscopy and its impact on patient recovery time and hospital discharge time.

Methods

Ninety-five patients undergoing hysteroscopy were randomly divided into two groups and received an initial dose of 0.2 mg/kg remimazolam tosilate (R group) and an initial dose of 2 mg/kg propofol (P group) as anesthetics during the examination. The primary end point was anesthesia recovery time (the time required for the patient’s MOAA/S score to reach 5 from the cessation of drug use) and hospital discharge time (the time required for the patient’s PADS score to reach 9 from the cessation of drug use). Secondary endpoints were first-dose sedation success rate, incidence of hypotension, and injection pain.

Results

Age(P =0.825), height(P =0.174), weight(P =0.667) and ASA grade (P =0.972) were not significantly different between the two groups. The recovery time in the R group was significantly shorter than that in the P group (P =0.019), and the data kurtosis in the R group was higher than that in the P group (1.19 vs −0.56), but there was no significant difference in the time to hospital discharge (P =0.696). There was no significant difference in the success rate of the first dose of sedation between the two groups (P =0.362), but the incidence of hypotension during anesthesia (P =0.001) and the incidence of injection pain (P =0.001) in the R group was significantly lower than those in P group.

Conclusions

Remimazolam tosilate is suitable for hysteroscopy anesthesia and can reduce intraoperative hypotension and injection pain during the examination, a more optimal dosage or target-controlled infusion model still needs to be further explored.
A Structural Proteome Screen Identifies Protein Mimicry in Host-Microbe Systems
Authors: Penunuri Gabriel , Wang Pingting , Corbett-Detig Russell , Russell Shelbi L
Published: April 2024

Host-microbe systems are evolutionary niches that produce coevolved biological interactions and are a key component of global health. However, these systems have historically been a difficult field of biological research due to their experimental intractability. Impactful advances in global health will be obtained by leveragingin silicoscreens to identify genes involved in mediating interspecific interactions. These predictions will progress our understanding of these systems and lay the groundwork for futurein vitroandin vivoexperiments and bioengineering projects. A driver of host-manipulation and intracellular survival utilized by host-associated microbes is molecular mimicry, a critical mechanism that can occur at any level from DNA to protein structures. We applied protein structure prediction and alignment tools to explore host-associated bacterial structural proteomes for examples of protein structure mimicry. By leveraging theLegionella pneumophilaproteome and its many known structural mimics, we developed and validated a screen that can be applied to virtually any host-microbe system to uncover signals of protein mimicry. These mimics represent candidate proteins that mediate host interactions in microbial proteomes. We successfully applied this screen to other microbes with demonstrated effects on global health,Helicobacter pyloriandWolbachia, identifying protein mimic candidates in each proteome. We discuss the roles these candidates may play in importantWolbachia-induced phenotypes and show thatWobachiainfection can partially rescue the loss of one of these factors. This work demonstrates how a genome-wide screen for candidates of host-manipulation and intracellular survival offers an opportunity to identify functionally important genes in host-microbe systems.
In Silico Generation of Gene Expression profiles using Diffusion Models
Authors: Lacan Alice , André Romain , Sebag Michele , Hanczar Blaise
Published: April 2024

Motivation

RNA-seq data is used for precision medicine (e.g., cancer predictions), which benefits from deep learning approaches to analyze complex gene expression data. However, transcriptomics datasets often have few samples compared to deep learning standards. Synthetic data generation is thus being explored to address this data scarcity. So far, only deep generative models such as Variational Autoencoders (VAEs) and Generative Adversarial Networks (GANs) have been used for this aim. Considering the recent success of diffusion models (DM) in image generation, we propose the first generation pipeline that leverages the power of said diffusion models.

Results

This paper presents two state-of-the-art diffusion models (DDPM and DDIM) and achieves their adaptation in the transcriptomics field. DM-generated data of L1000 landmark genes show better predictive performance over TCGA and GTEx datasets. We also compare linear and nonlinear reconstruction methods to recover the complete transcriptome. Results show that such reconstruction methods can boost the performances of diffusion models, as well as VAEs and GANs. Overall, the extensive comparison of various generative models using data quality indicators shows that diffusion models perform best and second-best, making them promising synthetic transcriptomics generators.

Availability and implementation

Data processing and full code available at:https://forge.ibisc.univevry.fr/alacan/rna-diffusion.git

Contact

alice.lacan@univ-evry.fr

Supplementary information

Supplementary data are available atBioRxivonline.
Brilacidin, a novel antifungal agent againstCryptococcus neoformans
Authors: Diehl Camila , Pinzan Camila Figueiredo , de Castro Patrícia Alves , Delbaje Endrews , Carnero Laura C. García , Sánchez-León Eddy , Bhalla Kabir , Kronstad James W. , Kim Dong-gyu , Doering Tamara L. , Alkhazraji Sondus , Mishra Nagendra N. , Ibrahim Ashraf S. , Yoshimura Mami , Isuhuaylas Luis Alberto Vega , Pham Lien Thi Kim , Yashiroda Yoko , Boone Charles , dos Reis Thaila Fernanda , Goldman Gustavo H.
Published: April 2024

Cryptococcus neoformanscauses cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug againstC. neoformans. BRI is able to affect the organization of the cell membrane, increasing fungal cell permeability. We also investigated the effects of BRI against the model systemSaccharomyces cerevisiaeby analyzing libraries of mutants grown in the presence of BRI. InS. cerevisiae, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism.In vivoexperiments show BRI significantly reducesC. neoformanssurvival inside macrophages and partially clearsC. neoformanslung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action againstC. neoformans. BRI+CAS affects endocytic movement, calcineurin, and mitogen activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.

Importance

Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts,Cryptococcus neoformansandCryptococcus gattii. There are few therapeutic options for treating cryptococcosis and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent againstC. neoformans. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth ofC. neoformans, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI+CAS againstC. neoformans. We propose BRI as a new antifungal agent against cryptococcosis.
Application of a High-Resolution Melt Assay for Monitoring SARS-CoV-2 Variants in Burkina Faso and Kenya
Authors: Greenland-Bews Caitlin , Shah Sonal , Achieng Morine , Badoum Emilie S. , Bah Yaya , Barsosio Hellen C. , Brazal-Monzó Helena , Canizales Jennifer , Drabko Anna , Fraser Alice J , Hannan Luke , Jarju Sheikh , Kaboré Jean-Moise , Kujabi Mariama A. , Lesosky Maia , Manneh Jarra , Marlais Tegwen , Matthewman Julian , Nebié Issa , Onyango Eric , Ouedraogo Alphonse , Otieno Kephas , Serme Samuel S. , Sirima Sodiomon , Soulama Ben , Tangara Brian , Tiono Alfred , Wu William , Sesay Abdul Karim , Soulama Issiaka , Kariuki Simon , Drakeley Chris , ter Kuile Feiko O , Adams Emily R , Allen David J , Edwards Thomas
Published: April 2024

The rapid emergence and global dissemination of SARS-CoV-2 highlighted a need for robust, adaptable surveillance systems. However, financial and infrastructure requirements for whole genome sequencing (WGS) mean most surveillance data have come from higher-resource geographies, despite unprecedented investment in sequencing in low-middle income countries (LMICs) throughout the SARS-CoV-2 pandemic. Consequently, the molecular epidemiology of SARS-CoV-2 in some LMICs is limited, and there is a need for more cost-accessible technologies to help close data gaps for surveillance of SARS-CoV-2 variants. To address this, we have developed two high-resolution melt curve (HRM) assays that target key variant-defining mutations in the SARS-CoV-2 genome, which give unique signature profiles that define different SARS-CoV-2 variants of concern (VOCs). Extracted RNA from SARS-CoV-2 positive samples collected from 205 participants (112 in Burkina Faso, 93 in Kenya) on the day of enrolment in the MALCOV study (Malaria as a Risk Factor for COVID-19) between February 2021 and February 2022 were analysed using our optimised HRM assays and compared to Next Generation Sequencing (NGS) on Oxford Nanopore MinION . With NGS as a reference, two HRM assays, HRM-VOC-1 and HRM-VOC-2, demonstrated sensitivity/specificity of 100%/99.29% and 92.86/99.39%, respectively, for detecting Alpha, 90.08%/100% and 92.31%/100% for Delta and 93.75%/100% and 100%/99.38% for Omicron. The assays described here provide a lower-cost approach (<$1 per sample) to conducting molecular epidemiology, capable of high-throughput testing. We successfully scaled up the HRM-VOC-2 assay to screen a total of 506 samples from which we were able to show the replacement of Alpha with the introduction of Delta and the replacement of Delta by the Omicron variant in this community in Kisumu, Kenya. These assays are readily adaptable and can focus on local epidemiological surveillance questions or be updated quickly to accommodate the emergence of a novel variant or adapt to novel and emerging pathogens.
Identifying risk factors for Lassa fever infection in Sierra Leone, 2019-2021
Authors: Sama Daniel Juma , Haider Najmul , Guitian Javier , Osman Abdinasir Yusuf , Ntoumi Francine , Zumla Alimuddin , Kock Richard , Ansumana Rashid
Published: April 2024

Background

Lassa fever (LF) virus (LASV) is endemic in Sierra Leone and poses a significant public health threat to the region; however, no risk factors for LASV infection have been reported in Sierra Leone. The objective of this study was to identify the risk factors for LASV infection in an endemic community in Sierra Leone.

Methods

We conducted a case-control study by enrolling 37 laboratory-confirmed LF cases identified through the national LF surveillance system in Sierra Leone, and 140 controls resided within a one-kilometre radius of the case household. We performed conditional multiple logistic regression analysis to identify the risk factors for LASV infection.

Results

Of the 37 cases enrolled, 23 died (62% case fatality rate). Cases were younger than controls (19.5 years vs 28.9 years, p<0.05) and more frequently female (64.8% vs. 52.8%). Compared to the controls, LF cases had contact with rodents (rats or mice) in their households more frequently in the preceding three weeks (83.8% vs.47.8%). Households with a cat reported a lower presence of rodents (73% vs 38%, p<0.01) and contributed to a lower rate of LF (48.6% vs 55.7%) although not statistically significant (p=0.56). The presence of rodents in the households (Matched Adjusted Odds Ratio [mAOR]: 11.1), and younger age (mAOR: 0.99) were independently associated with LASV infection.

Conclusion

Rodent access to households is likely a key risk factor for LASV infection in rural Sierra Leone and potentially in other countries within the West African region. Controlling rodent access to households might help reduce household-level LASV infection in Sierra Leone.
Micronutrient deficiencies and the double burden of malnutrition in Vietnamese female adolescents: a national cross-sectional study in 2020
Authors: Tan Xiaomian , Tan Pui Yee , Som Somphos Vicheth , Nguyen Son Duy , Tran Do Thanh , Tran Nga Thuy , Tran Van Khanh , Moore J. Bernadette , Gong Yun Yun
Published: April 2024

Background

Vietnam is facing a double burden of malnutrition, with increasing prevalence of overweight coexisting with undernutrition (stunting or thinness) and micronutrient deficiencies (MNDs). Although malnutrition during female adolescence leads to poor health outcomes with potential intergenerational effects on offspring, no studies have comprehensively investigated MNDs and nutritional status among contemporary Vietnamese female adolescents.

Methods

Data from 10-to 18-year-old female participants (n=1,471) in the nationally-representative Vietnam General Nutrition Survey 2020 were analysed. Blood nutritional biomarkers, anthropometric measurements, and socio-demographic data were collected and the associations between nutrition status and MNDs were analysed; with anaemia, iron deficiency (ID), iron deficiency anaemia, low serum zinc, low serum retinol, and any MNDs as specified outcomes.

Findings

Prevalence of overweight, stunting, and thinness was 27·2%, 14·3%, and 6·9%, respectively. Low serum zinc was common (39·8%), as was ID (9·8%). Bivariate analyses showed that older age (16-18 years old), ethnic minority, lower wealth index, and inflammation were associated with MNDs. In adjusted logistic regressions, stunting was associated with increased odds ratio (AOR) and [95% confidence intervals] of low serum retinol (8·92 [2·26, 35·15], p<0·01), as was thinness (12·25 [3·47, 43·33], p<0·01). Stunting was also associated with increased odds of having any MNDs (1·88 [1·13, 3·12], p<0·05).

Interpretation

More female adolescents were overweight than undernourished in Vietnam in 2020. However, undernutrition, low serum zinc, and ID remain prevalent. Food systems approaches should be considered to stem the stark increase in the double burden of malnutrition in young people living in Vietnam.

Funding

UK BBSRC BB/T008989/1.
Optimizing Antidepressant Efficacy: Generalizable Multimodal Neuroimaging Biomarkers for Prediction of Treatment Response
Authors: Tong Xiaoyu , Zhao Kanhao , Fonzo Gregory A. , Xie Hua , Carlisle Nancy B. , Keller Corey J. , Oathes Desmond J. , Sheline Yvette , Nemeroff Charles B. , Trivedi Madhukar , Etkin Amit , Zhang Yu
Published: April 2024

Major depressive disorder (MDD) is a common and often severe condition that profoundly diminishes quality of life for individuals across ages and demographic groups. Unfortunately, current antidepressant and psychotherapeutic treatments exhibit limited efficacy and unsatisfactory response rates in a substantial number of patients. The development of effective therapies for MDD is hindered by the insufficiently understood heterogeneity within the disorder and its elusive underlying mechanisms. To address these challenges, we present a target-oriented multimodal fusion framework that robustly predicts antidepressant response by integrating structural and functional connectivity data (sertraline: R2= 0.31; placebo: R2= 0.22). Remarkably, the sertraline response biomarker is further tested on an independent escitalopram-medicated cohort of MDD patients, validating its generalizability (p = 0.01) and suggesting an overlap of psychopharmacological mechanisms across selective serotonin reuptake inhibitors. Through the model, we identify multimodal neuroimaging biomarkers of antidepressant response and observe that sertraline and placebo show distinct predictive patterns. We further decompose the overall predictive patterns into constitutivenetwork constellationswith generalizable structural-functional co-variation, which exhibit treatment-specific association with personality traits and behavioral/cognitive task performance. Our innovative and interpretable multimodal framework provides novel and reliable insights into the intricate neuropsychopharmacology of antidepressant treatment, paving the way for advances in precision medicine and development of more targeted antidepressant therapeutics.

Trial Registration

Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC), NCT#01407094
On the parameterization of mathematical models of infectious disease transmission structured by age at the start of the epidemic spread
Authors: Sarratea Santiago , Fabricius Gabriel
Published: April 2024

Estimation of transmission and contact rate parameters among individuals in different age groups is a key point in the mathematical modeling of infectious disease transmission. Several approaches exist for this task but, given the complexity of the problem, the obtained values are always approximate estimations that hold in particular conditions. Our goal is to contribute to this task in the event of an emerging disease. We propose a methodology to estimate the contact rate parameters from the fraction of the incidence reported in each age group at the beginning of the epidemic spread. Working with an age-structured SIR model, we obtain an equation that relates the contact parameters to various epidemiological quantities that could be accessible through different sources. We apply the method to obtain information about the contact structure by age during the COVID-19 epidemic spread in Greater Buenos Aires (Argentina) in 2020. As we have the fractions of reported incidence by age but only rough estimations of other quantities involved in the method, we define several epidemiological scenarios based on various hypotheses. Using the different sets of contact parameters obtained, we evaluate control strategies and analyze the dependence of the results on our assumptions. The proposed method could be useful to obtain a fast first insight of a new emergent disease at the beginning of epidemic spread using the accessible information.
Social-semantic knowledge in frontotemporal dementia and after anterior temporal lobe resection
Authors: Rouse Matthew , Halai Ajay , Ramanan Siddharth , Rogers Timothy , Garrard Peter , Patterson Karalyn , Rowe James , Lambon Ralph Matthew
Published: April 2024

Degraded semantic memory is a prominent feature of frontotemporal dementia (FTD). It is classically associated with semantic dementia and anterior temporal lobe (ATL) atrophy, but semantic knowledge can also be compromised in behavioural-variant FTD (bvFTD). Motivated by understanding behavioural change in FTD, recent research has focused selectively on social-semantic knowledge, with proposals that the right ATL is specialised for social concepts. Previous studies have assessed very different types of social concepts and have not compared performance to that on matched non-social concepts. Consequently, it remains unclear to what extent various social concepts are (i) concurrently impaired in FTD, (ii) distinct from general semantic memory and (iii) differentially supported by the left and right ATL. This study assessed multiple aspects of social-semantic knowledge and general conceptual knowledge across cohorts with ATL-damage arising from either neurodegeneration or resection. We assembled a test battery measuring knowledge of multiple types of social concept. Performance was compared to non-social general conceptual knowledge, measured using the Cambridge Semantic Memory Test Battery and other matched non-social-semantic tests. Our transdiagnostic approach included bvFTD, semantic dementia and mixed intermediate cases to capture the FTD clinical spectrum, as well as age-matched healthy controls. People with unilateral left or right ATL resection for temporal lobe epilepsy (TLE) were also recruited to assess how selective damage to the left or right ATL impacts social- and non-social-semantic knowledge. Social- and non-social-semantic deficits were severe and highly correlated in FTD. Much milder impairments were found after unilateral ATL resection, with no left vs. right differences in social-semantic knowledge or general semantic processing, and with only naming showing a greater deficit following left vs. right damage. A principal component analysis of all behavioural measures in the FTD cohort extracted three components, interpreted as capturing: (1) FTD severity, (2) semantic memory and (3) executive function. Social and non-social measures both loaded heavily on the same semantic memory component, and scores on this factor were uniquely associated with bilateral ATL grey matter volume but not with the degree of ATL asymmetry. Together, these findings demonstrate that both social- and non-social-semantic knowledge degrade in FTD (semantic dementia and bvFTD) following bilateral ATL atrophy. We propose that social-semantic knowledge is part of a broader conceptual system underpinned by a bilaterally-implemented, functionally-unitary semantic hub in the ATLs. Our results also highlight the value of a transdiagnostic approach for investigating the neuroanatomical underpinnings of cognitive deficits in FTD.
The recurrence of illness (ROI) index is a key factor in major depression that indicates increasing immune-linked neurotoxicity and vulnerability to suicidal behaviors
Authors: Maes Michael , Jirakran Ketsupar , Vasupanrajit Asara , Niu Mengqi , Zhou Bo , St. Stoyanov Drozdstoj , Tunvirachaisakul Chavit
Published: April 2024

Background

The first author of this paper introduced new precision nomothetic models for a major depressive episode (MDD) which incorporate quantitative scores that measure recurrence of illness (ROI).

Objective

To explore the connections between ROI and biomarkers related to an activated immune network, immune-linked neurotoxicity (INT), and a combined INT and atherogenicity index (METAMMUNE).

Methods

The study involved 67 healthy controls and 66 outpatient MDD (OMDD) participants. We utilized a Multiplex method to measure 48 cytokines, and developed INT and METAMMUNE composite scores. The measurements included triglycerides, free cholesterol, LDL and HDL-cholesterol, apolipoprotein (Apo)A1 and ApoB.

Results

A ROI index was successfully created by extracting a validated principal component, from the number of physician-rated depressive episodes, the frequency of lifetime suicidal ideation and attempts. Adverse childhood experiences accounted for 20-22% of the variance in ROI. The latter was significantly associated with INT and METAMMUNE indices, neuroticism, lifetime and current suicidal behaviors, and the phenome (p<0.001). Our analysis revealed that a significant portion (55.1%) of the variance in the OMDD phenome, which includes current suicidal behaviors, anxiety, and depression, can be accounted for by the regression on INT, ROI, and emotional neglect and abuse. A validated latent construct was successfully extracted from the three ROI components, INT and METAMMUNE indices.

Conclusions

ROI and associated immune-metabolic biomarkers are indicators of a shared underlying concept, specifically a ROI-neuroimmune-metabolic pathway phenotype. ROI is a crucial indicator of the rising immune-metabolic abnormalities and heightened susceptibility to suicidal tendencies and recurrence of illness.
Exploring the causal effect of placental physiology in susceptibility to mental and addictive disorders: a Mendelian randomization study
Authors: Jácome-Ferrer Pablo , Costas Javier
Published: April 2024

Background

Epidemiological studies have linked low birth weight to psychiatric disorders, including substance use disorders. Genomic analyses suggest a role of placental physiology on psychiatric risk. We investigated whether this association is causally related to impaired trophoblast function.

Methods

We conducted a two-sample summary-data Mendelian randomization study using as instrumental variables genetic variants strongly associated with birth weight, whose effect is exerted through the fetal genome, and are located near genes with differential expression in trophoblasts. Eight psychiatric and substance use disorders with >10,000 samples were included as outcomes. The inverse variance weighted method was used as the main analysis and several sensitivity analyses were performed for those significant results.

Results

The inverse variance weighted estimate, based on 14 instrumental variables, revealed an association, after correction for multiple tests, between birth weight and broadly-defined depression (beta=-0.165, 95% CI=-0.282 to -0.047, P=0.0059). Sensitivity analyses revealed absence of heterogeneity in the effect of instrumental variables, confirmed by leave-one-out analysis, MR_Egger intercept and MR_PRESSO. The effect was consistent using robust methods. Reverse causality was not detected. The effect was specifically linked to genetic variants near genes involved in trophoblast physiology instead of genes with fetal effect on birth weight or involved in placenta development.

Conclusion

Impaired trophoblast functioning, probably leading to reduced fetal brain oxygen and nutrient supply, is causally related to broadly-defined depression. Considering the therapeutic potential of some agents to treat fetal growth restriction, further research on the effect of trophoblast physiology on mental disorders may have future implications in prevention.