bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genetic variation in Fucosyltransferase 8 accelerates HIV-1 disease progression indicating a role for N-glycan fucosylation
Authors: van Pul Lisa , Maurer Irma , Boeser-Nunnink Brigitte D.M. , Harskamp Agnes M. , van Dort Karel A. , Kootstra Neeltje A. 
Published: August 2023

Objectives:
Core fucosylation by fucosyltransferase 8 (FUT8) is an important post-translational modification that impacts components of the immune system. Genetic variations in FUT8 can alter its function and could therefore play a role in the anti-viral immune response and pathogenesis of HIV-1. This study analyzed the effect of a single nucleotide polymorphism (SNP) in FUT8 on the clinical course of HIV-1 infection.

Design/methods:
The effect of SNPs in FUT8 on untreated HIV-1 disease outcome were analyzed in a cohort of 304 people with HIV-1 (PWH) using survival analysis. Flow-cytometry was used to determine the effect of SNP on T-cell activation, differentiation and exhaustion/senescence. T-cell function was determined by proliferation assay and by measuring intracellular cytokine production. The effect of the SNP on HIV-1 replication was determined by in-vitro HIV-1 infections. Sensitivity of HIV-1 produced in PBMC with or without the SNP to broadly neutralizing antibodies was determined using a TZM-bl based neutralization assay.

Results:
Presence of the minor allele of SNP rs4131564 was associated with accelerated disease progression. The SNP had no effect on T-cell activation and T cell differentiation in PWH. Additionally, no differences in T cell functionality as determined by proliferation and cytokine production was observed. HIV-1 replication and neutralization sensitivity was also unaffected by the SNP in FUT8.

Conclusions:
SNP rs4131564 in FUT8 showed a major impact on HIV-1 disease course underscoring a role for N-glycan fucosylation even though no clear effect on the immune system or HIV-1 could be determined in vitro.
Modelling morbidity for neglected tropical diseases: the long and winding road from cumulative exposure to long-term pathology
Authors: Borlase Anna , Prada Joaquin M. , Crellen Thomas 
Published: August 2023

Reducing the morbidities caused by neglected tropical diseases (NTDs) is a central aim of ongoing disease control programmes. The broad spectrum of pathogens under the umbrella of NTDs lead to a range of negative health outcomes, from malnutrition and anaemia to organ failure, blindness and carcinogenesis. For some NTDs, the most severe clinical manifestations develop over many years of chronic or repeated infection. For these diseases, the association between infection and risk of long-term pathology is generally complex, and the impact of multiple interacting factors, such as age, co-morbidities and host immune response, is often poorly quantified. Mathematical modelling has been used for many years to gain insights into the complex processes underlying the transmission dynamics of infectious diseases; however, long-term morbidities associated with chronic or cumulative exposure are generally not incorporated into dynamic models for NTDs. Here we consider the complexities and challenges for determining the relationship between cumulative pathogen exposure and morbidity at the individual and population levels, drawing on case studies for trachoma, schistosomiasis and foodborne trematodiasis. We explore potential frameworks for explicitly incorporating long-term morbidity into NTD transmission models, and consider the insights such frameworks may bring in terms of policy-relevant projections for the elimination era.This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Lymphatic filariases and soil-transmitted helminthiases in Sri Lanka: the challenge of eliminating residual pockets of transmission
Authors: Chandrasena Nilmini T. G. A. , Gunaratna I. E. , Ediriweera Dileepa , de Silva N. R. 
Published: August 2023

Sri Lanka has successfully met the challenge of controlling both lymphatic filariasis (LF) and soil-transmitted helminthiases (STH) as public health problems. The primary public health strategy for combatting both conditions has been preventive chemotherapy. The national programme for the elimination of LF implemented five annual rounds of mass chemotherapy in the endemic districts from 2002 to 2006 using a combination of diethylcarbamazine and albendazole. The overall microfilaria rate declined from 0.21% in 2001 before the mass chemotherapy, to 0.06% in 2016, at declaration of elimination of LF as a public health problem by the World Health Organization. Currently Sri Lanka is in the phase of post-validation surveillance. Achieving control of STH has been more difficult. Mass deworming programmes have been implemented for nearly a century, and national-level surveys reported prevalence rates declining from 6.9% in 2003 to 1% in 2017. However, neither of these infections has been completely eliminated. A situation analysis indicates continued transmission of both among high-risk communities. This paper explores the reasons for persistence of transmission of both LF and STH in residual pockets and the measures that are required to achieve long-term control, or perhaps even interrupt transmission in Sri Lanka.
This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
A positive consequence of the COVID-19 pandemic: how the counterfactual experience of school closures is accelerating a multisectoral response to the treatment of neglected tropical diseases
Authors: Bundy Donald A. P. , Schultz Linda , Antoninis Manos , Barry Fatoumata B. M. , Burbano Carmen , Croke Kevin , Drake Lesley , Gyapong John , Karutu Carol , Kihara Jimmy , Lo Mouhamadou Moustapha , Makkar Prerna , Mwandawiro Charles , Ossipow Suzy J. , Bento Ana Ramos , Rollinson David , Shah Hemang , Turner Hugo C. 
Published: August 2023

Global access to deworming treatment is one of the public health success stories of low-income countries in the twenty-first century. Parasitic worm infections are among the most ubiquitous chronic infections of humans, and early success with mass treatment programmes for these infections was the key catalyst for the neglected tropical disease (NTD) agenda. Since the launch of the ‘London Declaration’ in 2012, school-based deworming programmes have become the world's largest public health interventions. WHO estimates that by 2020, some 3.3 billion school-based drug treatments had been delivered. The success of this approach was brought to a dramatic halt in April 2020 when schools were closed worldwide in response to the COVID-19 pandemic. These closures immediately excluded 1.5 billion children not only from access to education but also from all school-based health services, including deworming. WHO Pulse surveys in 2021 identified NTD treatment as among the most negatively affected health interventions worldwide, second only to mental health interventions. In reaction, governments created a global Coalition with the twin aims of reopening schools and of rebuilding more resilient school-based health systems. Today, some 86 countries, comprising more than half the world's population, are delivering on this response, and school-based coverage of some key school-based programmes exceeds those from January 2020. This paper explores how science, and a combination of new policy and epidemiological perspectives that began in the 1980s, led to the exceptional growth in school-based NTD programmes after 2012, and are again driving new momentum in response to the COVID-19 pandemic.This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Global prioritization of endemic zoonotic diseases for conducting surveillance in domestic animals to protect public health
Authors: Qiu Yu , Guitian Javier , Webster Joanne P. , Musallam Imadidden , Haider Najmul , Drewe Julian A. , Song Junxia 
Published: August 2023

Zoonotic diseases (zoonoses) originating from domestic animals pose a significant risk to people's health and livelihoods, in addition to jeopardizing animal health and production. Effective surveillance of endemic zoonoses at the animal level is crucial to assessing the disease burden and risk, and providing early warning to prevent epidemics in animals and spillover to humans. Here we aimed to prioritize and characterize zoonoses for which surveillance in domestic animals is important to prevent human infections at a global scale. A multi-criteria qualitative approach was used, where disease-specific information was obtained across literature of the leading international health organizations. Thirty-two zoonoses were prioritized, all of which have multi-regional spread, cause unexceptional human infections and have domestic animal hosts as important sources or sentinels of zoonotic infections. Most diseases involve multiple animal hosts and/or modes of zoonotic transmission, where a lack of specific clinical signs in animals further complicates surveillance. We discuss the challenges of animal health surveillance in endemic and resource-limited settings, as well as potential avenues for improvement such as the multi-disease, multi-sectoral and digital surveillance approaches. Our study will support global capacity-building efforts to strengthen the surveillance and control of endemic zoonoses at their animal sources.
This article is part of the theme issue ‘Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs’.
Determinants of Bluetooth-enabled Self Measured Blood Pressure monitoring in Federally Qualified Health Centers
Authors: Hellem Abby , Whitfield Candace , Mansour Maria , Curran Yvonne , Dinh Mackenzie , Warden Kimberly , Skolarus Lesli 
Published: August 2023

AbstractBackgroundIn 2021, the Health Resources and Services Administration (HRSA) launched the National Hypertension Control Initiative (HTN Initiative) with the goal to enhance HTN control through Bluetooth-enabled self-measured blood pressure (BT SMBP) monitoring and use this data to inform clinical decisions in Federally Qualified Health Centers (FQHCs) with large proportion of their population with uncontrolled BP. We sought to understand the experience of Michigan-based FQHCs in implementing the HTN initiative.MethodsStaff from three Michigan-based FQHCs were invited to participate in semi-structured interviews from September to November 2022. Interviews were conducted in-person and were based on the Tailored Implementation of Chronic Diseases framework. Content analysis was performed by three coders.ResultsTen staff participated in interviews (FQHC 1: n=6, FQHC 2: n=1, FQHC 3: n=3). The FQHCs differed in their stage of implementation and their approach. FQHC 1 created a large-scale, community health worker driven program, FQHC 2 created a small-scale, short term, BP device loan program, and FQHC 3 created a primarily outsourced, large-scale program through a contracted partner. Positive staff attitudes and outcome expectations, previous experience with SMBP grants, and supportive clinic leadership were identified as facilitators to implementation; Patients high social needs, SMBP-related Technology, and insufficient workforce and staff capacity were identified as barriers.ConclusionBT SMBP among FQHC patients is promising but challenges in integrating SMBP data into clinic workflow, workforce capacity to support the high social needs of participants and to assist in reacting to the more frequent BP data remain to be overcome.
Deep Learning Enhanced Tandem Repeat Variation Identification via Multi-Modal Conversion of Nanopore Reads Alignment
Authors: Liao Xingyu , Zhou Juexiao , Zhang Bin , Xu Xiaopeng , Li Haoyang , Gao Xin 
Published: August 2023

AbstractIdentification of tandem repeat (TR) variations plays a crucial role in advancing our understanding of genetic diseases, forensic analysis, evolutionary studies, and crop improvement, thereby contributing to various fields of research and practical applications. However, traditional TR identification methods are often limited to processing genomes obtained through sequence assembly and cannot directly start detection from sequencing reads. Furthermore, the inflexibility of detection mode and parameters hinders the accuracy and completeness of the identification, rendering the results unsatisfactory. These shortcomings result in existing TR variation identification methods being associated with high computational cost, limited detection sensitivity, precision and comprehensiveness. Here, we propose DeepTRs, a novel method for identifying TR variations, which enables direct TR variation identification from raw Nanopore sequencing reads and achieves high sensitivity, accuracy, and completeness results through the multi-modal conversion of Nanopore reads alignment and deep learning. Comprehensive evaluations demonstrate that DeepTRs outperform existing methods.
Helper NLRs Nrc2 and Nrc3 act co-dependently with Prf/Pto and activate MAPK signaling to induce immunity in tomato
Authors: Zhang Ning , Gan Joyce , Carneal Lauren , González-Tobón Juliana , Filiatrault Melanie , Martin Gregory B. 
Published: August 2023

AbstractPlant intracellular immune receptors, primarily nucleotide-binding, leucine-rich repeat proteins (NLRs), can detect virulence proteins (effectors) from pathogens and activate NLR-triggered immunity (NTI). Recently, ‘sensor’ NLRs have been reported to function with ‘helper’ NLRs to activate immune responses. We investigated the role of two helper NLRs, Nrc2 (NLR required for cell death 2) and Nrc3, on immunity in tomato to the bacterial pathogenPseudomonas syringaepv.tomato(Pst) mediated by the sensor NLR Prf and the Pto kinase. Loss-of-function mutations in bothNrc2andNrc3completely compromised Prf/Pto-mediated NTI toPstcontaining the cognate effectors AvrPto and AvrPtoB. Annrc3mutant showed intermediate susceptibility between wild-type tomato plants and aPrfmutant, while annrc2mutant developed only mild disease symptoms. These observations indicate that Nrc2 and Nrc3 act additively to contribute to Prf/Pto-mediated immunity. We also examined at what point Nrc2 and Nrc3 act in the Prf/Pto-mediated immune response. In thenrc2/3mutant, programmed cell death (PCD) normally induced by constitutively-active variants of AvrPtoB, Pto or Prf was abolished, but that induced by M3Kα or Mkk2 was not. PCD induced by a constitutively active variant of Nrc3 was also abolished in aNicotiana benthamianaline with reduced expression ofPrf. MAPK activation triggered by expression of AvrPto in the wild-type Pto-expressing tomato plants was completely abolished in thenrc2/3 mutant. These results indicate that Nrc2 and Nrc3 act in concert with Prf/Pto and upstream of MAPK signaling. Nrc2 and Nrc3 were not required for the HR triggered by Ptr1, another sensor NLR mediatingPstresistance, although these helper NLRs do appear to be involved in resistance to certainPstrace 1 strains.
Irreversible PDMS bonding using flame activation of adhesives for fabrication of microfluidic and organ-on-chip devices
Authors: Singer Ryan , Hirota Jeremy A. , Dabaghi Mohammadhossein 
Published: August 2023

AbstractPolydimethylsiloxane (PDMS) is widely used for microfluidics fabrication in many disciplines due to its ease of use in soft lithography and its ability to bond liquid-tight seals. A variety of PDMS-PDMS bonding methods exist, but each may have limitations for some applications. For example, chemical bonding via oxygen plasma treatment is reliable but requires expensive equipment and specialized training. Here we present a rapid, low-cost, and accessible method for irreversible PDMS bonding in which flame treatment activates PDMS and Nitto 5302A adhesive surfaces. Using this technique, PDMS microchannels can be fabricated with a bonding integrity of up to 325 kPa burst pressure. This technique is suitable for fabricating organ-on-chip devices for cell line and primary cell culture, supporting cell viability and establishment of key cellular features in apical and basal compartments, while maintaining bonding integrity.
Ehrlichia chaffeensisco-opts phagocytic hemocytes for systemic dissemination in the Lone Star tick,Amblyomma americanum
Authors: Adegoke Abdulsalam , Hanson Julia , Smith Ryan , Karim Shahid 
Published: August 2023

AbstractHematophagous arthropods can acquire and transmit several pathogens of medical importance. In ticks, the innate immune system is crucial in the outcome between vector-pathogen interaction and overall vector competence. However, the specific immune response(s) elicited by the immune cells known as hemocytes remains largely undefined inEhrlichiachaffeensisand its competent tick vector,Amblyomma americanum. Here, we show that granulocytes, professional phagocytic cells, are integral in eliciting immune responses against commensal and pathogen infection. The chemical depletion of granulocytes led to decreased phagocytic efficiency of tissues-associated hemocytes. We demonstrateE. chaffeensiscan infect circulating hemocytes, and both cell-free plasma and hemocytes fromE. chaffeensis-infected ticks can establishEhrlichiainfection in recipient ticks. Lastly, we provide evidence to show granulocytes play a dual role inE. chaffeensisinfection. Depleting granulocytic hemocytes increasedEhrlichiaload in the salivary gland and midgut tissues. In contrast, granulocyte depletion led to a reduced systemic load ofEhrlichia. This study has identified multiple roles for granulocytic hemocytes in the control and systemic dissemination ofE. chaffeensisinfection.
Trabeculations of the porcine and human cardiac ventricles are different in number but similar in total volume
Authors: Jensen Bjarke , Salvatori Daniela , Schouten Jacobine , Meijborg Veronique M. F. , Lauridsen Henrik , Agger Peter 
Published: August 2023

AbstractAn intricate meshwork of trabeculations lines the luminal side of cardiac ventricles. Compaction, a developmental process, is thought to reduce trabeculations by adding them to the neighboring compact wall which is then enlarged. When pig, a plausible cardiac donor for xenotransplantation, is compared to human, the ventricular walls appear to have fewer trabeculations. We hypothesized the trabecular volume is proportionally smaller in pig than in human. Macroscopically, we observed in sixteen pig hearts that the ventricular walls harbor few but large trabeculations. Close inspection revealed a high number of tiny trabeculations, a few hundred, within the recesses of the large trabeculations. While tiny, these were still larger than embryonic trabeculations and even when considering their number, the total tally of trabeculations in pig was much fewer than in human. Volumetrics based on high-resolution MRI of additional six pig hearts compared to six human hearts, revealed the left ventricles were not significantly differently trabeculated (21.5 versus 22.8%, respectively), and the porcine right ventricles were only slightly less trabeculated (42.1 versus 49.3%, respectively). We then analyzed volumetrically ten pig embryonic hearts from gestational day 14 to 35. The trabecular and compact layer always grew, as did the intertrabecular recesses, in contrast to what compaction predicts. The proportions of the trabecular and compact layers changed substantially, nonetheless, due to differences in their growth rate rather than compaction. In conclusion, processes that affect the trabecular morphology do not necessarily affect the proportion of trabecular-to-compact myocardium and they are then distinct from compaction.
Long noncoding RNAs and mRNAs profiling in ovary during laying and broodiness in Taihe Black-Bone Silky Fowls (Gallus gallus domesticus Brisson)
Authors: Tan Yuting , Huang Yunyan , Xu Chunhui , Huang Xuan , Yin Zhaozheng 
Published: August 2023

AbstractBroodiness is one of the important factors affecting poultry egg production, with the black-bone Silky (Gallus gallus domesticus Brisson) exhibiting strong broodiness behavior. Changes in ovarian signaling can offer insights into the mechanisms influencing broodiness. However, research comparing the characteristics of long non- coding RNAs (lncRNAs) in the ovaries during the broody chickens (BC) and high egg- laying chickens (GC) groups of poultry is still limited. In this study, we employed RNA-seq to analyze the ovarian transcriptomes (lncRNAs and mRNAs) of eight brooding and high egg-laying Taihe Black-Bone Silky Fowls (TBsf). We identified a total of 16,444 mRNAs and 18,756 lncRNAs, among which 349 mRNAs and 651 lncRNAs (P < 0.05) showed significantly different expression (DE) between the BC and GC groups. Additionally, we identified the cis-regulated and trans-regulated target genes of differentially abundant lncRNA transcripts and constructed an lncRNA- mRNA trans-regulated interaction network associated with ovarian follicle development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation analyses revealed that DE mRNAs and target genes of DE lncRNAs were associated with neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, Cytokine-cytokine receptor interaction, and ECM-receptor interaction pathways. Our study provides a catalogue of lncRNAs and mRNAs related to ovarian development and constructs a predicted interaction network of differentially abundant lncRNAs and Differentially Expressed Genes (DEGs) in TBsf, thus enhancing our understanding of the interactions between lncRNAs and genes regulating brooding behavior.Author summaryIn this study, we performed transcriptome sequencing analysis of the ovaries from BC and GC groups in TBsf. A total of 349 significantly differentially expressed mRNAs and 651 significantly differentially expressed lncRNAs were detected. Furthermore, we identified 10 key genes that may affect reproductive performance in chickens: STC1, MMP13, IL8, AT2, FSHB, RARB, THOC7, FGF12, EPHA1, and NPY5R. Based on GO and KEGG enrichment analyses, we preliminarily explored five pathways that may influence egg production performance: neuroactive ligand-receptor interaction, CCR6 chemokine receptor binding, G-protein coupled receptor binding, cytokine-cytokine receptor interaction and ECM-receptor interaction. These genes and pathways may play crucial roles in improving broodiness behavior. This study establishes a foundation for subsequent screening of candidate functional genes and functional validation of important production traits in TBsf, providing a theoretical basis for further molecular breeding and enhancing egg-laying performance in TBsf.
Bioengineering of a human innervated cardiac muscle model
Authors: Schneider Lennart Valentin , Guobin Bao , Methi Aditi , Jensen Ole , Schmoll Kea Aline , Setya Michael Gani , Sakib Sadman , Fahud Aminath Luveysa , Brockmöller Jürgen , Fischer André , Liaw Norman Y. , Zimmermann Wolfram-Hubertus , Zafeiriou Maria-Patapia 
Published: August 2023

AbstractCardiac autonomic neurons control cardiac contractility. Dysregulation of the autonomic nervous system can lead to sympathetic overdrive resulting in heart failure and an increased incidence of fatal arrhythmias. Here, we introduce innervated engineered human myocardium (iEHM), a novel model of neuro-cardiac junctions, constructed by fusion of a bioengineered neural organoid (BENO) patterned to autonomic nervous system and engineered human myocardium (EHM). Projections of sympathetic neurons into engineered human myocardium formed presynaptic terminals in close proximity to cardiomyocytes and an extensive vascular network co-developing in the tissues. Contractile responses to optogenetic stimulation of the accordingly engineered neuronal component demonstrated functionality of neuro-cardiac junctions in iEHM. This model will serve as a human surrogate system to delineate neuron and cardiac cell contribution to brain and heart diseases and is an important step towards engineering a human brain to heart axis in a dish.