bluuebunny/crossref_metadata_2025 huggingface dataset:
Current international tools and guidance for the implementation of hand hygiene recommendations in community settings: a scoping review
Authors: MacLeod Clara , Esteves Mills Joanna , Caruso Bethany A , Chase Claire , Chidziwisano Kondwani , Chipungu Jenala , Dreibelbis Robert , Ejemot-Nwadiaro Regina , Gordon Bruce , Thomas Ann , Cumming Oliver , Braun Laura
Published: May 2024

Background

Hand hygiene is an important measure to prevent disease transmission. This scoping review identifies and summarises current tools and guidance for the implementation of hand hygiene recommendations in community settings.

Methods

We conducted a scoping review following the Arksey and O’Malley framework. To identify relevant documents, we searched: 1) a grey literature database, 2) Google search engine, and 3) the websites of international organisations in August 2023. We included tools and implementation guidance relevant to hand hygiene in community settings, categorised as domestic, public, or institutional, and published in English by international organisations between January 1990 and August 2023. Tools and implementation guidance were mapped to an existing conceptual framework adapted for this review that includes a six-step implementation approach.

Results

We included a total of 35 documents, comprising 30 implementation guidance documents and 5 stand-alone tools. Among these 35 documents, we identified 207 implementation recommendations and a total of 21 tools for the six implementation steps. The 21 tools include 5 stand-alone tools and 16 tools embedded within guidance documents. Most implementation guidance was mapped to steps 1 (prepare for action), 2 (analyse the situation), 3 (develop an action plan), and 5 (monitor, evaluate, and course correct) of the conceptual framework, with limited guidance for step 4 (executing the action plan) and step 6 (cross-cutting themes). Over half of identified tools are for step 2 (analyse the situation) and primarily for undertaking a situation analysis. Only two documents provided guidance or a tool across the six steps.

Conclusion

Implementation guidance is available, yet inconsistently spread across the different implementation steps. There is also a limited number of tools to support implementation. Future work should focus on developing comprehensive practical tools for the implementation of hand hygiene recommendations in community settings, in line with international guidelines.
Glutathione Effects on Liver Enzymes and Serum Electrolyte in Mice Exposed to 850–1900 MHz Mobile Phone Radiation
Authors: Binhambali Abdulhakeem , Umar Abdullahi Hussein , Aliyah Ahmed Temitayo , Mukhtar Abubakar Ibrahim , Tekanyi Amat Abdoulie , Pate Aisha Ahmad , Nuhu Amina , Ipinlaiye Tolulope , Muhammad Haruna Kolo , Ismail Ummulkhairi , Magaji Rabiu AbduSSALAM
Published: May 2024

The widespread presence of electromagnetic fields (EMF) produced by modern technologies may pose a significant threat to animal health. Ionizing radiation, a byproduct of EMF exposure, has the potential to contribute to serious diseases, including cancer. This study examines the impact of chronic exposure to 900-1800 MHz GSM-EMF-induced electromagnetic radiation on liver enzymes and serum electrolytes in mice, and the potential mitigating effects of exogenous glutathione (GSH) administration. Thirty-five adult male mice were randomly divided into seven groups and exposed to various modes of mobile phone radiation for five weeks, with or without GSH administration. Liver enzymes, Alkaline phosphates (ALP), Alanine transaminase (ALT), Aspartate aminotransferase (AST) and, serum electrolytes, sodium, potassium and bicarbonate were analyzed. Results showed significant increases in ALP levels in the Silent, Ringtone + GSH, and Silent + GSH groups compared to control group, while ALT and AST levels remained largely unchanged with the exception of some groups across the experimental cohorts. Serum electrolyte concentrations did not significantly differ across the control group. Our study found that chronic mobile phone radiation exposure in mice generally does not significantly affect liver enzyme levels or serum electrolyte concentrations. However, certain combinations with GSH administration notably increased some biochemical markers like ALP, ALT, and AST levels. Our study concluded that chronic mobile phone radiation had no significant impact on liver enzymes or serum electrolytes in mice. However, glutathione administration in combination with radiation increased liver enzyme levels, suggesting a potential role in oxidative stress mitigation. Further research is needed to explore these findings.
Bone marrow by day, lymph nodes by night: Undernutrition imparts a distinct circadian rhythm to T cells in mice
Authors: Foster Takesha R. , Dadzie Kwesi A. , Dunn Sydney , Gubbels Bupp Melanie R.
Published: May 2024

In well-nourished organisms, T cells migrate between the blood and secondary lymphoid organs, conducting surveillance for invading pathogens. T cell surveillance is under circadian control via diurnal fluctuations in corticosterone levels and undernutrition is associated with increased corticosterone. Therefore, we hypothesized that undernutrition disrupts the circadian migratory patterns of T cells. We report that compared to well-nourished controls, undernourished mice demonstrate enhanced T cell relocation to the bone marrow throughout the 24-hour period, but especially during the light phase, and diminished T cell migration to the lymph nodes only during the light phase. Undernutrition-related changes in T cell expression of key migration proteins are also mostly limited to the light phase. For example, undernourished naïve CD4+ T cells exhibited higher levels of CXCR4 and CCR7 as well as reduced levels of S1P1 compared to controls; with all changes, except for CXCR4 expression, being restricted to the light phase. These results suggest that naïve CD4+ T cells in the lymph nodes upregulate CXCR4 during the dark phase, enabling their migration to the bone marrow where they remain for the light phase. Once there, CCR7 is upregulated, presumably sending them back to the lymph node, thereby preserving immunosurveillance during the dark phase. Naïve CD4+ T cell disengagement from S1P1-related egress signals may further contribute to increased retention of cells within each compartment during the appropriate phase. Undernutrition-related increases in T cell residency of the bone marrow likely preserve T cell numbers until nutrition is restored.
Maggot : An ecosystem for sharing metadata within the web of FAIR Data
Authors: Jacob Daniel , Ehrenmann François , David Romain , Tran Joseph , Mirande-Ney Cathleen , Chaumeil Philippe
Published: May 2024

Background

Descriptive metadata are crucial for the discovery, reporting and mobilisation of research datasets. Addressing all metadata issues within the Data Management Plan often poses challenges for data producers. Organising and documenting data within data storage entails creating various descriptive metadata. Subsequently, data sharing involves ensuring metadata interoperability in alignment with FAIR principles. Given the tangible nature of these challenges, a real need for management tools has to be addressed to assist data managers to the fullest extent. Moreover, these tools have to meet data producers requirements and be user-friendly as well with minimal training as prerequisites.

Results

We developed Maggot which stands for Metadata Aggregation on Data Storage, specifically designed to annotate datasets by generating metadata files to be linked into storage spaces. Maggot enables users to seamlessly generate and attach comprehensible metadata to datasets within a collaborative environment. This approach seamlessly integrates into a data management plan, effectively tackling challenges related to data organisation, documentation, storage, and frictionless FAIR metadata sharing within the collaborative group and beyond. Furthermore, for enabling metadata crosswalk, metadata generated with Maggot can be converted for a specific data repository or configured to be exported into a suitable format for data harvesting by third-party applications.

Conclusion

The primary feature of Maggot is to ease metadata capture based on a carefully selected schema and standards. Then, it greatly eases access to data through metadata as requested nowadays in projects funded by public institutions and entities such as Europe Commission. Thus, Maggot can be used on one hand to promote good local versus global data management with open data sharing in mind while respecting FAIR principles, and on the other hand to prepare the future EOSC FAIR Web of Data within the framework of the European Open Science Cloud.
Serum Proteome Profiling Identifies N-Cadherin and C-Met as Early Marker Candidates of Therapeutic Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Steenbuck Ines Derya , Cosenza-Contreras Miguel , Fröhlich Klemens , Mayer Bettina , Kurowski Konrad , Werner Tilman , Reinold Meike , Fahrner Matthias , Hause Frank , Seredynska Adrianna , Feilen Tobias , Ritter Andrea , Guénégou-Arnoux Armelle , Biniossek Martin L. , Weiss Daniela , Nöthling Claudia , Jäger Markus , Erbes Thalia , Schilling Oliver
Published: May 2024

Breast cancer remains the most common cancer in women worldwide. Neoadjuvant chemotherapy (NACT) is often preferred to adjuvant chemotherapy to achieve tumour shrinkage, monitor response to therapy and facilitate surgical removal in the absence of metastases. In addition, there is strong evidence that pathological complete remission (pCR) is associated with prolonged survival. In this study, we sought to identify candidate markers that signal response or resistance to therapy. We present a retrospective longitudinal serum proteomic study of 22 breast cancer patients (11 with pCR and 11 with non-pCR) matched with 21 healthy controls. Serum was analysed by LC-MS/MS after depletion of abundant proteins by immunoaffinity, trypsinisation, isobaric labelling and fractionation by reversed-phase HPLC. We observed an inverse behaviour of the serum proteins c-Met and N-cadherin after the second cycle of chemotherapy with a high predictive value (AUC 0.93). More pronounced changes were observed after the 6th cycle of NACT, with significant changes in the intensity of the proteins contactin-1, centrosomal protein, sex hormone-binding globuline and cholinesterase. Our study highlights the possibility of monitoring response to NACT using serum as a liquid biopsy.
micronuclAI: Automated quantification of micronuclei for assessment of chromosomal instability
Authors: Ibarra-Arellano Miguel A. , Caprio Lindsay A. , Hada Aroj , Stotzem Niklas , Cai Luke , Shah Shivem , Melms Johannes C. , Wünneman Florian , Izar Benjamin , Schapiro Denis
Published: May 2024

Chromosomal instability (CIN) is a hallmark of cancer that drives metastasis, immune evasion and treatment resistance. CIN results from chromosome mis-segregation events during anaphase, as excessive chromatin is packaged in micronuclei (MN), that can be enumerated to quantify CIN. Despite recent advancements in automation through computer vision and machine learning, the assessment of CIN remains a predominantly manual and time-consuming task, thus hampering important work in the field. Here, we presentmicronuclAI, a novel pipeline for automated and reliable quantification of MN of varying size, morphology and location from DNA-only stained images. InmicronucleAI, single-cell crops are extracted from high-resolution microscopy images with the help of segmentation masks, which are then used to train a convolutional neural network (CNN) to output the number of MN associated with each cell. The pipeline was evaluated against manual single-cell level counts by experts and against routinely used MN ratio within the complete image. The classifier was able to achieve a weighted F1 score of 0.937 on the test dataset and the complete pipeline can achieve close to human-level performance on various datasets derived from multiple human and murine cancer cell lines. The pipeline achieved a root-mean-square deviation (RMSE) value of 0.0041, an R2of 0.87 and a Pearson’s correlation of 0.938 on images obtained at 10X magnification. We tested the approach in otherwise isogenic cell lines in which we genetically dialed up or down CIN rates, and also on a publicly available image data set (obtained at 100X) and achieved an RMSE value of 0.0159, an R2of 0.90, and a Pearson’s correlation of 0.951. Given the increasing interest in developing therapies for CIN-driven cancers, this method provides an important, scalable, and rapid approach to quantifying CIN on routinely obtained images. We release a GUI-implementation for easy access and utilization of the pipeline.
Comprehensive analysis of microbial content in whole-genome sequencing samples from The Cancer Genome Atlas project
Authors: Ge Yuchen , Lu Jennifer , Puiu Daniela , Revsine Mahler , Salzberg Steven L.
Published: May 2024

In recent years, a growing number of publications have reported the presence of microbial species in human tumors and of mixtures of microbes that appear to be highly specific to different cancer types. Our recent re-analysis of data from three cancer types revealed that technical errors have caused erroneous reports of numerous microbial species found in sequencing data from The Cancer Genome Atlas (TCGA) project. Here we have expanded our analysis to cover all 5,734 whole-genome sequencing (WGS) data sets currently available from TCGA, covering 25 distinct types of cancer. We analyzed the microbial content using updated computational methods and databases, and compared our results to those from two major recent studies that focused on bacteria, viruses, and fungi in cancer. Our results expand upon and reinforce our recent findings, which showed that the presence of microbes is far smaller than had been previously reported, and that many species identified in TCGA data are either not present at all, or are known contaminants rather than microbes residing within tumors. As part of this expanded analysis, and to help others avoid being misled by flawed data, we have released a dataset that contains detailed read counts for bacteria, viruses, archaea, and fungi detected in all 5,734 TCGA samples, which can serve as a public reference for future investigations.

One-sentence summary

Analysis of microbial content in 5,734 whole-genome sequencing samples from TCGA yields a comprehensive new resource for investigating the role of microbes in cancer.
DNA damage causes ATM-dependent heterochromatin loss leading to nuclear softening, blebbing, and rupture
Authors: Eskndir Nebiyat , Hossain Manseeb , Currey Marilena L , Pho Mai , Berrada Yasmin , Stephens Andrew D
Published: May 2024

The nucleus must maintain stiffness to protect the shape and integrity of the nucleus to ensure proper function. Defects in nuclear stiffness caused from chromatin and lamin perturbations produce abnormal nuclear shapes common in aging, heart disease, and cancer. Loss of nuclear shape via protrusions called blebs leads to nuclear rupture that is well-established to cause nuclear dysfunction, including DNA damage. However, it remains unknown how increased DNA damage affects nuclear stiffness, shape, and ruptures, which could create a negative feedback loop. To determine if increased DNA damage alters nuclear physical properties, we treated MEF cells with DNA damage drugs cisplatin and bleomycin. DNA damage drugs caused increased nuclear blebbing and rupture in interphase nuclei within a few hours and independent of mitosis. Micromanipulation force measurements reveal that DNA damage decreased chromatin-based nuclear mechanics but did not change lamin-based strain stiffening at long extensions relative to wild type. Immunofluorescence measurements of DNA damage treatments reveal the mechanism is an ATM-dependent decrease in heterochromatin leading to nuclear weaken, blebbing, and rupture which can be rescued upon ATM inhibition treatment. Thus, DNA damage drugs cause ATM-dependent heterochromatin loss resulting in nuclear softening, blebbing, and rupture.
Mitochondrial Calcium Signaling Regulates Branched-Chain Amino Acid Catabolism in Fibrolamellar Carcinoma
Authors: Marsh Nicole M. , MacEwen Melissa J. S. , Chea Jane , Kenerson Heidi L. , Kwong Albert A. , Locke Timothy M. , Miralles Francisco Javier , Sapre Tanmay , Gozali Natasha , Hart Madeleine L. , Bammler Theo K. , MacDonald James W. , Sullivan Lucas B. , Atilla-Gokcumen G. Ekin , Ong Shao-En , Scott John D. , Yeung Raymond S. , Sancak Yasemin
Published: May 2024

Metabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter plays a key role in coordinating metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation, and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial pathways has remained unexplored. Here, we investigate metabolic consequences of uniporter loss- and gain-of-function using uniporter knockout cells and the liver cancer fibrolamellar carcinoma (FLC), which we demonstrate to have elevated mitochondrial calcium levels. Our results reveal that branched-chain amino acid (BCAA) catabolism and the urea cycle are uniporter-regulated metabolic pathways. Reduced uniporter function boosts expression of BCAA catabolism genes, and the urea cycle enzyme ornithine transcarbamylase (OTC). In contrast, high uniporter activity in FLC suppresses their expression. This suppression is mediated by reduced expression of the transcription factor KLF15, a master regulator of liver metabolism. Thus, uniporter responsive calcium signaling plays a central role in FLC-associated metabolic changes, including hyperammonemia. Our study identifies an important role for mitochondrial calcium signaling in metabolic adaptation through transcriptional regulation of metabolism and elucidates its importance for BCAA and ammonia metabolism in FLC.
Researcher and Clinician Preferences for a Journal Transparency Tool: A Mixed-Methods Survey and Focus Group Study
Authors: Ng Jeremy Y. , Liu Henry , Masood Mehvish , Kochhar Jassimar , Moher David , Ehrlich Alan , Iorio Alfonso , Cobey Kelly D.
Published: May 2024

Background

Transparency within biomedical research is essential for research integrity, credibility, and reproducibility. To increase adherence to optimal scientific practices and enhance transparency, we propose the creation of a journal transparency tool (JTT) that will allow users to obtain information about a given scholarly journal’s operations and transparency policies. This study is part of a program of research to obtain user preferences to inform the proposed JTT. Here, we report on our consultation with clinicians and researchers.

Methods

This mixed-methods study was conducted in two parts. The first part involved a cross-sectional survey conducted on a random sample of authors from biomedical journals. The survey asked clinicians and researchers about the inclusion of a series of potential scholarly metrics and user features in the proposed JTT. Quantitative survey items were summarized with descriptive statistics. Thematic content analysis was employed to analyze text-based responses. Subsequent focus groups used the survey responses to further explore the inclusion of items in the JTT. Items with less than 70% agreement were used to structure discussion points during these sessions. Participants voted on the use of user features and metrics to be considered within the journal tool after each discussion. Thematic content analysis was conducted on interview transcripts to identify the core themes discussed.

Results

A total of 632 participants (5.5% response rate) took part in the survey. A collective total of 74.7% of respondents found it either ‘occasionally, ‘often’, or ‘almost always’ difficult to determine if health information online is based on reliable research evidence.

Twenty-two participants took part in the focus groups. Three user features and five journal tool metrics were major discussion points during these sessions. Thematic analysis of interview transcripts resulted in six themes. The use of registration was the only item to not meet the 70% threshold after both the survey and focus groups. Participants demonstrated low scholarly communication literacy when discussing tool metric suggestions.

Conclusions

Our findings suggest that the JTT would be valuable for both researchers and clinicians. The outcomes of this research will contribute to developing and refining the tool in accordance with researchers and clinicians.
Implementation of an Enhanced Medication Access Workflow within a Health System Specialty Pharmacy: Impact on Patient & Clinician Experience
Authors: Harkonen Brandon , Cuttitta Anthony , Henderson James , Gavrila Valerie , Mckibbin Jey , Luttman Sherrie , Benedict Wendy , Kelley Lindsey R. , Flanders Scott A. , Choe Hae Mi , Barnes Geoffrey D
Published: May 2024

Purpose

The initiation of specialty medications is associated with patient access challenges and clinician burden. This intervention invested resources upstream of the prescription being written. The evaluation assessed the impact on patient and clinician experience.

Methods

The specialty pharmacy intervention was designed to improve medication access within five medical specialty clinics by utilizing an embedded medication access team assigned to patients and prescribers of targeted medications. We used a multi-methods evaluative approach. Semi-structured qualitative interviews provided an understanding of clinician experience. To quantitatively assess associations between the referral process and patient experience, we analyzed the emotional valence of patient portal messages using a retrospective cohort study and an event study framework of a non-randomized, stepped wedge implementation design.

Results

The intervention was associated with an increase in the net positive emotional valence of patient portal messages (AME, 5.3; 95% CI, 3.8-6.8). Except for gastroenterologists seeing patients for irritable bowel disease, patients cared for in all other specialties experienced statistically significant increases in net positive valence in the primary analysis. Regarding clinician experience, four major interrelated themes emerged from 17 qualitative interviews with prescribers and pharmacists: (1) decreased clinician burden, general praise, (2) improved experience & satisfaction, reduced anxiety & concerns, (3) rewarding praise for other prescribers/colleagues, and (4) excellent coordination, efficiency, and speed.

Conclusion

Investing staff resources before, during, and after the prior authorization process greatly improves clinician experience. The positive valence of patient portal messages also increased suggesting patient experience improvements.
Advancing Sewage Sample Surveillance with OmiCrisp: A CRISPR-Based Platform for Variant-Specific SARS-CoV-2 Detection
Authors: Kruthika BS , Roy Bidipta , Shridhar Varsha , Gupta Vaijayanti , Chandru Vijay , Arora Reety
Published: May 2024

The detection and differentiation of SARS-CoV-2 variants are vital for disease management and timely patient isolation. Although qRT-PCR has been the standard method, our OmiCrisp assay has shown superior results in identifying Omicron and non-Omicron variants. The World Health Organization advises ongoing sewage surveillance to monitor community viral load, accounting for both symptomatic and asymptomatic individuals. In a previous study, our CRISPR-based assay achieved a 99% concordance with qRT-PCR in sewage samples. We expanded this research by analyzing 182 sewage samples from Bangalore during the JN.1 (BA.2.86.1.1) variant outbreak. Using the OmiCrisp assay, 153 samples (84.06%) tested positive, 16 (8.79%) were negative, and 13 (7.14%) were low positive. Results indicated a significant reduction in positivity rates by the end of the study. The OmiCrisp assay thus proves to be an accurate and effective tool for community-wide surveillance of SARS-CoV-2 variants.
Pentavalent Vaccine: How Safe Is It Among Infants Accessing Immunization In Nigerian Health Facilities
Authors: Elemuwa Uchenna Geraldine , Ehijie Enato , Elemuwa Christopher Ononiwu , Elemuwa Tochukwu Daniel , Raimi Morufu Olalekan
Published: May 2024

Rationale: Pentavalent vaccines offer significant public health benefits by protecting against five major diseases with a single injection. However, concerns have been raised in various studies regarding potential associations between combined vaccines and conditions such as autism, febrile seizures, sudden unexpected death in infancy, demyelinating disorders, and neurodevelopmental disorders. Objective: This study aimed to evaluate the safety of pentavalent vaccines administered to infants aged between 6 and 14 weeks. Methods: A total of 423 infants, all aged 6 weeks and receiving their first pentavalent vaccine at selected healthcare facilities, were recruited for the study after obtaining informed consent from their mothers or caregivers. The infants were administered three doses of the vaccine at 6, 10, and 14 weeks. Mothers and caregivers were provided with diaries and thermometers to monitor and record any Adverse Events Following Immunization (AEFI) observed in their babies after each vaccine dose. Follow-up was conducted through telephone calls to ensure accurate monitoring and recording of any identified events. Results: The study identified various AEFIs in the infants following their routine immunizations. These included pain at the injection site, fever, swelling at the injection site, vomiting, refusal to feed, excessive crying, coughing, rash, stooling, restlessness, and severe local reactions. Fever was the most commonly reported systemic AEFI, with incidence rates decreasing from 66.98% after the first dose to 55.37% after the third dose. Pain and swelling at the injection site were the most frequently reported local AEFIs, with their incidence also decreasing from the first to the third doses. No statistically significant differences were observed in the occurrence of AEFIs across the three doses. Conclusions: The pentavalent vaccine was found to be safe for infants in the Federal Capital Territory (FCT), Nigeria, with the observed AEFIs being generally mild and decreasing in frequency with subsequent doses. Recommendations: Further studies should be conducted to monitor long-term safety and potential rare adverse effects of pentavalent vaccines. Additionally, public health education should emphasize the safety and benefits of pentavalent vaccines to increase vaccination rates and reduce vaccine hesitancy. Significance Statement: This study underscores the safety of pentavalent vaccines in infants, reinforcing their role in preventing multiple serious diseases through a single immunization schedule. The findings support the continued use and promotion of pentavalent vaccines in public health programs, particularly in regions with high infant mortality rates and limited healthcare resources.
The Longevity Landscape: Value Creation for Healthy Aging
Authors: Mekniran Wasu , Giger Odile-Florence , Fleisch Elgar , Kowatsch Tobias , Jovanova Mia
Published: May 2024

Background

The global aging population underscores a critical need to tackle accompanying health and economic challenges, at all levels of society. ThisAll-of-Societyapproach emphasizes the involvement of various stakeholders—governments, NGOs, researcher centers, private companies, local communities, and opinion leaders—to collectively promote healthy aging. However, how stakeholders enable healthy longevity remains unclear.

Objective

This study examines how global stakeholders (governments, NGOs, researcher centers, private companies, local communities, and opinion leaders) create value towards healthy longevity. We identify the healthy longevity dimension of stakeholders’ value propositions and examine alignment between their propositions as an indicator of shared goals.

Methods

Following theAll-of-Societyapproach, we analyzed the healthy longevity aspects of value propositions among the six classes of stakeholders (N=128). We (1) employed semantic topic modeling to identify the primary value proposition topics as related to healthy longevity and (2) computed proposition alignment using similarity networks.

Results

Our analysis revealed varying degrees of alignment between stakeholders’ healthy longevity propositions, with the lowest alignment observed for local communities and researcher centers.

Conclusions

Findings underscore a key need to strengthen synergies between academic and community-based initiatives to promote translational science and highlight opportunities for strategic partnerships in the evolving healthy longevity field.

What is already known on this topic

The National Academy of Medicine’sAll-of-Societyapproach advocates for multi-stakeholder engagement towards healthy longevity, but specific stakeholder contributions, and their alignment toward shared goals, are poorly understood.

What this study adds

To our knowledge, this study is the first to provide empirical evidence into the value propositions of healthy longevity stakeholders on a societal scale. It highlights key areas where multi-stakeholder collaboration can be strengthened—particularly between academic and local community initiatives—and proposes five strategies to strengthen collaboration.

How this study might affect research, practice, or policy

Prioritizing (1) community-based participatory research, (2) translating healthy aging-related research findings into accessible resources, (3) prioritizing equity in intervention delivery, (4) establishing community advisory boards, and (5) developing knowledge translation and training programs, could potentially better align academic and community efforts towards more aligned, equitable and effective healthy longevity initiatives.
Enhancing the Diagnostic Utility of ASL Imaging in Temporal Lobe Epilepsy through FlowGAN: An ASL to PET Image Translation Framework
Authors: Lucas Alfredo , Vadali Chetan , Mouchtaris Sofia , Arnold T. Campbell , Gugger James J. , Kulick-Soper Catherine , Josyula Mariam , Petillo Nina , Das Sandhitsu , Dubroff Jacob , Detre John A. , Stein Joel M. , Davis Kathryn A.
Published: May 2024

Background and Significance

Positron Emission Tomography (PET) using fluorodeoxyglucose (FDG-PET) is a standard imaging modality for detecting areas of hypometabolism associated with the seizure onset zone (SOZ) in temporal lobe epilepsy (TLE). However, FDG-PET is costly and involves the use of a radioactive tracer. Arterial Spin Labeling (ASL) offers an MRI-based quantification of cerebral blood flow (CBF) that could also help localize the SOZ, but its performance in doing so, relative to FDG-PET, is limited. In this study, we seek to improve ASL’s diagnostic performance by developing a deep learning framework for synthesizing FDG-PET-like images from ASL and structural MRI inputs.

Methods

We included 68 epilepsy patients, out of which 36 had well lateralized TLE. We compared the coupling between FDG-PET and ASL CBF values in different brain regions, as well as the asymmetry of these values across the brain. We additionally assessed each modality’s ability to lateralize the SOZ across brain regions. Using our paired PET-ASL data, we developed FlowGAN, a generative adversarial neural network (GAN) that synthesizes PET-like images from ASL and T1-weighted MRI inputs. We tested our synthetic PET images against the actual PET images of subjects to assess their ability to reproduce clinically meaningful hypometabolism and asymmetries in TLE.

Results

We found variable coupling between PET and ASL CBF values across brain regions. PET and ASL had high coupling in neocortical temporal and frontal brain regions (Spearman’sr >0.30, p < 0.05) but low coupling in mesial temporal structures (Spearman’sr <0.30, p > 0.05). Both whole brain PET and ASL CBF asymmetry values provided good separability between left and right TLE subjects, but PET (AUC = 0.96, 95% CI: [0.88, 1.00]) outperformed ASL (AUC = 0.81; 95% CI: [0.65, 0.96]). FlowGAN-generated images demonstrated high structural similarity to actual PET images (SSIM = 0.85). Globally, asymmetry values were better correlated between synthetic PET and original PET than between ASL CBF and original PET, with a mean correlation increase of 0.15 (95% CI: [0.07, 0.24],p<0.001, Cohen’sd= 0.91). Furthermore, regions that had poor ASL-PET correlation (e.g. mesial temporal structures) showed the greatest improvement with synthetic PET images.

Conclusions

FlowGAN improves ASL’s diagnostic performance, generating synthetic PET images that closely mimic actual FDG-PET in depicting hypometabolism associated with TLE. This approach could improve non-invasive SOZ localization, offering a promising tool for epilepsy presurgical assessment. It potentially broadens the applicability of ASL in clinical practice and could reduce reliance on FDG-PET for epilepsy and other neurological disorders.
High acceptability of newborn screening for sickle cell disease among post-natal mothers in western Kenya
Authors: Orimbo John , Awandu Shehu Shagari , Muhonja Faith , Owili Patrick , Omondi Dickens
Published: May 2024

Background

Sickle cell disease is a genetically inherited blood disorder that manifests early in life with resultant significant health complications. Globally, nearly three quarters of all affected babies are in sub-Saharan Africa. Early identification of babies with sickle cell disease through newborn screening followed by early linkage to care is recommended. However, the program has not been widely adopted in the sub-Saharan Africa. Evidence on acceptability of newborn screening to scale up newborn screening program is scarce. This study assessed factors associated with acceptability of newborn screening among mothers of newborns delivered at Homa Bay county teaching and referral hospital, western Kenya.

Methods

This study employed a cross-sectional design among postnatal mothers at Homa Bay county teaching and referral hospital with 399 postnatal mothers enrolled into the study. A semi-structured questionnaire was used for data collection. Maternal sociodemographic characteristics, knowledge, and perception were assessed. Babies were also screened for sickle cell disease using Sickle SCAN point-of-care test. The acceptability was calculated as percentage of mothers accepting to have their babies screened. Data were analyzed using logistic regression to explore factors associated with acceptability of newborn screening for sickle cell disease.

Results

Ninety-four percent of mothers accepted newborn screening for sickle cell disease. Mother’s age and occupation were significantly associated with acceptability of newborn screening for sickle cell disease. Younger mothers (OR=3.01;95%CI=1.16-7.83;p=0.024) and being a student (OR= 6.18; 95%CI= 1.18-32.22;p=0.031) were significant at bivariate regression analysis. Only being a student (aOR= 25.02; 95% CI=1.29-484.51; p= 0.033) was significant at multivariate logistic regression analysis.

Conclusion

The acceptability of newborn screening for sickle cell disease is high in the county. The Homabay county and the Kenyan ministry of health should implement routine newborn screening for sickle cell disease in all level 2-6 hospitals.
Impact of Dental Disorders on Self-rated dental Health Status of the Elderly in Selected Rural Communities in Kenya
Authors: Amulla Walter Ogutu , Njororai Fletcher
Published: May 2024

Low prioritization of oral care for the elderly and inadequacy of resources results in high prevalence of dental disorders in this population in most African countries. This study aimed at assessing the impact of self-rated dental health among the elderly in Kenya. A cross-sectional quantitative study was conducted among 300 subjects in parts of Karachuonyo sub-county of Homa Bay County, Kenya. The sample size was determined using Yamane’s formula based on a study population of 1159. Data was collected through interviewer-administered questionnaires. Majority (64%) of the respondents were aged 65-74 years. Female respondents were more (55.3%) than males (44.75). Further, 8 in 10 of the study sample never had any formal employment with nearly the same proportion (79.3%) self-rating their economic status as poor. Nearly 7 out of 10 (67%) respondents had lost at least one tooth due to medical extraction whereas half of the respondents (52.3%) were having at least one carious tooth at the time of data collection. Tooth loss had the strongest impact on self-rated dental health (X2=27.818, p<0.00001, φ = 0.305) followed by tooth mobility (X2=27.180,p<0.00001, φ = 0.301), gingival bleeding (X2=19.378, p=0.000011, φ = 0.254) and cavities (X2=17.757, p=0.000025, φ = 0.243). The study established that dental disorders significantly but disproportionately impacted self-rated dental health of the elderly, with tooth loss being the leading disorder. Increasing provision of services for the elderly for dental health needs is critical in Kenya as in most African countries.
Longitudinal Influenza A Virus Screening of Retail Milk from Canadian Provinces (Rolling Updates)
Authors: Wallace Hannah L. , Wight Jordan , Baz Mariana , Dowding Barbara , Flamand Louis , Hobman Tom , Jean Francois , Joy Jeffrey B , Lang Andrew S. , MacParland Sonya , McCormick Craig , Noyce Ryan , Russell Rodney S. , Sagan Selena M. , Snyman Jumari , Rzeszutek Gabriela J. , Jafri Mustafa S. , Bogoch Isaac , Kindrachuk Jason , Rasmussen Angela L.
Published: May 2024

Highly pathogenic avian influenza (HPAI) H5N1 has caused the deaths of more than 100 million birds since 2021, and human cases since 1997 have been associated with significant morbidity and mortality. Given the recent detection of HPAI H5N1 in dairy cattle and H5N1 RNA detections in pasteurized retail milk in the United States, we established the Pan-Canadian Milk (PCM) Network. Through our network of collaborators from across Canada, retail milk is being procured longitudinally and sent to a central laboratory for testing for the presence of influenza A virus RNA. To date (05 July 2024), we have tested 92 retail milk samples from all ten Canadian provinces (NL, NS, PEI, NB, QC, ON, MB, SK, AB, and BC) and all have tested negative for influenza A virus RNA. Testing is ongoing and these results will be updated on rolling basis as additional data becomes available. Despite no known HPAI infections of dairy cattle in Canada to date, H5N1 poses a significant threat to the health of both humans and other animals. Routine surveillance of retail milk on a national scale will allow for monitoring of infected dairy cattle on an ongoing basis in a cost-effective, standardized, scalable and easily accessible manner. Our network and testing will act as an early detection system to help inform containment and mitigation activities if positive samples are identified.
Utility of cerebrovascular imaging biomarkers to detect cerebral amyloidosis
Authors: Howe Matthew D. , Caruso Megan R. , Manoochehri Masood , Kunicki Zachary J. , Emrani Sheina , Rudolph James L. , Huey Edward D. , Salloway Stephen P. , Oh Hwamee ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2024

STRUCTURED ABSTRACT

INTRODUCTION

The relationship between cerebrovascular disease (CVD) and amyloid-β (Aβ) in Alzheimer disease (AD) is understudied. We hypothesized that magnetic resonance imaging (MRI)-based CVD biomarkers, including cerebral microbleeds (CMBs), ischemic infarction, and white matter hyperintensities (WMH), would correlate with Aβ positivity on positron emission tomography (Aβ-PET).

METHODS

We cross-sectionally analyzed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI, N=1,352). Logistic regression was used to calculate odds ratios (ORs), with Aβ-PET positivity as the standard-of-truth.

RESULTS

Following adjustment, WMH (OR=1.25) and superficial CMBs (OR=1.45) remained positively associated with Aβ-PET positivity (p<.001). Deep CMBs and infarcts exhibited a varied relationship with Aβ-PET in cognitive subgroups. The combined diagnostic model, which included CVD biomarkers and other accessible measures, significantly predicted Aβ-PET (pseudo-R2=.41).

DISCUSSION

The study highlights the translational value of CVD biomarkers in diagnosing AD, and underscores the need for more research on their inclusion in diagnostic criteria.ClinicalTrials.gov:ADNI-2 (NCT01231971), ADNI-3 (NCT02854033)
Mobility and non-household environments: understanding dengue transmission patterns in urban contexts
Authors: Peña-García Víctor Hugo , Ndenga Bryson A. , Mutuku Francis M. , Bisanzio Donal , LaBeaud A. Desiree , Mordecai Erin A.
Published: May 2024

Background

Households (HH) have been traditionally described as the main environments where people are at risk of dengue (and other arbovirus) infection. Mounting entomological evidence has suggested a larger role of environments other than HH in transmission. Recently, an agent-based model (ABM) estimated that over half of infections occur in non-household (NH) environments like workplaces, markets, and recreational sites. However, the importance of human and vector mobility and the configurations of urban spaces in mediating the effects of NH on dengue transmission remains understudied.

Methods

To improve our knowledge of the relevance of NH in transmission, we expanded an ABM calibrated from field data in Kenya to examine movement of people and vectors under different spatial configurations of buildings. In this model, we assessed the number of people traveling between HH and NH and their distance. Those were studied on three different urban configurations, on which the NH are spatially distributed either randomly (scattered), centered (in a single center), or clustered (in more than one cluster).

Results

Across simulations, the number of people moving is a major influential variable where higher levels of movement between HH and NH increases the number of cases. In addition, the number of cases is higher when NH are scattered. Intriguingly, the distance that people travel from HH to NH seems to have little effect on dengue burden; however, it affects the level of spatial clustering of cases.

Conclusions

These results highlight the importance of NH as a major spreader of infections between HH and NH environments supporting the relevance of NH in transmission and its interaction with human movement in driving dengue dynamics.
Accuracy of Combined Deep Learning Algorithms in Detecting Spontaneous Intracranial Hemorrhage on Emergent Head CT Scans
Authors: Juuso Takala , Heikki Peura , Pirinen Riku , Katri Väätäinen , Terjajev Sergei , Lin Ziyuan , Raj Rahul , Miikka Korja
Published: May 2024

Background

Spontaneous intracranial hemorrhages are life-threatening conditions that require fast and accurate diagnosis. We hypothesized that deep learning (DL) could be utilized to detect these hemorrhages with a high accuracy.

Methods

We developed a DL solution for detecting spontaneous intracerebral (ICH), intraventricular (IVH) and subarachnoid hemorrhages (SAH) from head non-contrast CT (NCCT) scans. The solution included four convolutional neural network (CNN) base models for different hemorrhage types and a CNN metamodel that was trained on top of the base models. We validated the performance of the solution by using a retrospective real-world dataset of consecutive emergency head NCCTs imaged during a 3-month period in 10 different hospitals. The head NCCTs with hemorrhages were stratified into groups by delay from symptom onset to NCCT imaging to better evaluate the suitability of the solution for emergency use.

Results

The real-world validation dataset included 7797 emergency head NCCTs that were imaged between October 1stand December 31st2021. Of these, 118 were reported to show spontaneous intracranial hemorrhages by on-call radiologists, and 7679 were reported negative for hemorrhages. The developed solution detected all reported 78 (sensitivity 100%) spontaneous intracranial hemorrhages if the head NCCT was presumably or confirmedly taken within 12 hours of symptom onset. When assessed for hemorrhages imaged 12 to 24 hours after symptom onset (13 cases), the sensitivity was 76.5 %. Overall sensitivity for detecting spontaneous intracranial hemorrhages on head NCCTs that were imaged with any delay from symptom onset was 89.8 %, and specificity was 89.5 %. The solution also detected five cases that were missed by on-call radiologists.

Conclusions

The DL solution showed high sensitivity for detecting spontaneous ICHs, IVHs and SAHs within the same time window in which also modern CT scanners work best for detecting acute blood on head NCCTs.
Analysis of Costs and Diagnostic Experience of Stroke Mimics at a Latin American University Hospital
Authors: Villalobos Ibarra Juan David , Carrizosa Jorge , Vargas Andrea , Martinez Carlos , Battaglini Denise , Godoy Daniel Agustin
Published: May 2024

Introduction

The incidence of stroke mimic symptoms is around 30%. These symptoms impact healthcare costs, often leading mimic stroke patients to undergo unnecessary clinical tests, imaging, and treatments.

Objectives

The main goal of this study is to describe the types of stroke mimic symptoms and estimate healthcare costs in patients with stroke mimics. Secondary objectives include comparing costs based on Telestroke Mimics Stroke and FABS scores and determining the frequency of thrombolysis.

Methods

We conducted a retrospective observational study. We reviewed medical records of all patients admitted to Fundación Santa Fe de Bogotá with a final diagnosis of ischemic stroke mimic. We characterized the study population and analyzed the costs of interventions in these patients.

Results

A total of 111 patients were included. The average age at mimic presentation was 65 ± 19.4 years, with transient ischemic attack (TIA) being the most common cause of mimics in both sexes, followed by migraine. Tissue plasminogen activator was administered in 0.9% of patients. The direct costs of activating the stroke code averaged US$1,098.72, with a cost of laboratory and imaging at US$773.95. The average cost of total hospitalization was US$2,220.16 per patient.

Conclusions

The most frequent cause of stroke mimic was TIA, and thrombolysis was performed in 0.9% of cases. The direct costs incurred by activating the stroke code, diagnostic tests, treatment with intravenous thrombolysis, and hospitalization of patients with stroke mimic are lower compared to other studies.
Transcriptome Analysis IdentifiedSPP1+Monocytes as a Key in Extracellular Matrix Formation in Thrombi
Authors: Kitano Takaya , Sasaki Tsutomu , Matsui Takahiro , Kohara Masaharu , Ogawa Kotaro , Kenichi Todo , Nakamura Hajime , Sugiura Yuri , Shimada Yuki , Okazaki Shuhei , Iida Junichi , Shimazu Kohki , Morii Eiichi , Sakaguchi Manabu , Nishio Masami , Yokoe Masaru , Kishima Haruhiko , Mochizuki Hideki
Published: May 2024

Thrombi follow various natural courses. They are known to become harder over time and may persist long-term; some of them can also undergo early spontaneous dissolution and disappearance. Hindering thrombus stability may contribute to the treatment of thrombosis and the prevention of embolisms. However, the detailed mechanisms underlying thrombus maturation remain unknown. Using RNA sequencing, we revealed the transcriptional landscape of thrombi retrieved from the cerebral vessels and identifiedSPP1as a hub gene related to extracellular matrix formation. Immunohistochemistry confirmed the expression of osteopontin in monocytes/macrophages in the thrombi, particularly in older thrombi. Single-cell RNA sequencing of thrombi from the pulmonary artery revealed increased communication betweenSPP1-high monocytes/macrophages and fibroblasts. These data suggest thatSPP1-high monocytes/macrophages play a crucial role in extracellular matrix formation in thrombi and provide a basis for new antithrombotic therapies targeting thrombus maturation.

Teaser

SPP1+monocytes play a key role in thrombus maturation, which can be a potential target for novel antithrombotic therapies.