bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of NRG1-VII: the myeloid-derived class of NRG1
Authors: Berrocal-Rubio Miguel A , Pawer Yair David Joseph , Dinevska Marija , De Paoli-Iseppi Ricardo , Widodo Samuel S. , Gleeson Josie , Rajab Nadia , De Nardo Will , Hallab Jeannette , Li Anran , Mantamadiotis Theo , Clark Michael B. , Wells Christine A.
Published: August 2024

The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.
Neural acetylcholinesterase and monoamine oxidase deregulation during streptozotocin-induced behavioral, metabolic and redox modification in Nauphoeta cinerea
Authors: Ogunsuyi Opeyemi B. , Olagoke Olawande C. , Famutimi Mayokun E. , Olatunde Damilola M. , Souza Diogo O. G. , Oboh Ganiyu , Barbosa Nilda V. , Rocha João B.T.
Published: August 2024

Genetic and environmental factors have been linked with neurodegeneration, especially in the elderly. Yet, efforts to impede neurodegenerative processes have at best addressed symptoms instead of underlying pathologies. The gap in the understanding of neuro-behavioral plasticity is consistent from insects to mammals, and cockroaches have been proven to be effective models for studying the toxicity mechanisms of various chemicals. We therefore used head injection of 74 and 740 nmol STZ in Nauphoeta cinerea to elucidate the mechanisms of chemical-induced neurotoxicity, as STZ is known to cross the blood-brain barrier. Neurolocomotor assessment was carried out in a new environment, while head homogenate was used to estimate metabolic, neurotransmitter and redox activities, followed by RT-qPCR validation of relevant cellular signaling. STZ treatment reduced the distance and maximum speed travelled by cockroaches, and increased glucose levels while reducing triglyceride levels in neural tissues. The activity of neurotransmitter regulators – AChE and MAO was exacerbated, with concurrent upregulation of glucose sensing and signaling, and increased mRNA levels of redox regulators and inflammation-related genes. Consequently, STZ neurotoxicity is conserved in insects, with possible implications for using N. cinerea to target the multi-faceted mechanisms of neurodegeneration and test potential anti-neurodegenerative agents.
Take-home naloxone administered in emergency settings: feasibility of intervention implementation in a cluster randomized trial
Authors: Snooks Helen A. , Jones Jenna K. , Bell Fiona B. , Benger Jonathon R. , Black Sarah L. , Dixon Simon , Edwards Adrian , Emery Helena , Evans Bridie A. , Fuller Gordon W. , Goodacre Steve , Hoskins Rebecca , Hughes Jane , John Ann , Johnston Sasha , Jones Matthew B. , Moore Chris R. , Parab Rakshita , Pilbery Richard , Sampson Fiona C. , Watkins Alan
Published: August 2024

Background

Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT).

Methods

We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019–2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events.

Results

At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported.

Conclusion

Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned.

Trial Registration

ISRCTN13232859 (Registered 16/02/2018).
Supporting treatment adherence for resilience and thriving (START): protocol for a mHealth randomized controlled trial
Authors: Davis-Ewart Leah , Atkins Lindsay , Ghanooni Delaram , Diaz José E. , Chuku Chika C. , Balise Raymond , DeVries Britt A. , Miller-Perusse Michael , Ackley III Donovan , Moskowitz Judith T. , McCollister Kathryn , Fardone Erminia , Hirshfield Sabina , Horvath Keith J. , Carrico Adam W.
Published: August 2024

Background

Although behavioral interventions show some promise for reducing stimulant use and achieving durable viral suppression in sexual minority men (SMM) with HIV, scalable mHealth applications are needed to optimize their reach and cost-effectiveness.

Methods

Supporting Treatment Adherence for Resilience and Thriving (START) is a randomized controlled trial (RCT) testing the efficacy and cost-effectiveness of a mHealth application that integrates evidence-based positive affect regulation skills with self-monitoring of adherence and mood. The primary outcome is detectable HIV viral load (i.e., > 300 copies/mL) from self-collected dried blood spot (DBS) specimens at 6 months. Secondary outcomes include detectable DBS viral load at 12 months, self-reported stimulant use severity, anti-retroviral therapy (ART) adherence, and positive affect over 12 months. A national sample of up to 250 SMM with HIV who screen positive for stimulant use disorder and reporting suboptimal ART adherence is being recruited via social networking applications through April of 2024. After providing informed consent, participants complete a run-in period (i.e., waiting period) including two baseline assessments with self-report measures and a self-collected DBS sample. Those who complete the run-in period are randomized to either the START mHealth application or access to a website with referrals to HIV care and substance use disorder treatment resources. Participants provide DBS samples at baseline, 6, and 12 months to measure HIV viral load as well as complete self-report measures for secondary outcomes at quarterly follow-up assessments over 12 months.

Discussion

To date, we have paid $117,500 to advertise START on social networking applications and reached 1,970 eligible participants ($59.77 per eligible participant). Although we identified this large national sample of potentially eligible SMM with HIV who screen positive for a stimulant use disorder and report suboptimal ART adherence, only one-in-four have enrolled in the RCT. The run-in period has proven to be crucial for maintaining scientific rigor and reproducibility of this RCT, such that only half of consented participants complete the required study enrollment activities and attended a randomization visit. Taken together, findings will guide adequate resource allocation to achieve randomization targets in future mHealth research SMM with HIV who use stimulants.

Trial Registration

This protocol was registered on clinicaltrials.gov (NCT05140876) on December 2, 2021.
Genomic variation in Plasmodium relictum (lineage SGS1) and its implications for avian malaria infection outcomes: insights from experimental infections and genome-wide analysis
Authors: Kalbskopf Victor , Aželytė Justė , Palinauskas Vaidas , Hellgren Olof
Published: August 2024

Background

The globally transmitted avian malaria parasite Plasmodium relictum (lineage SGS1) has been found to infect hundreds of different bird species with differences in infection outcomes ranging from more or less latent to potentially mortal. However, to date basic knowledge about the links between genetic differentiation and variation in infection outcome within this single malaria parasite species is lacking.

Methods

In this study, two different isolates of SGS1, obtained in the wild from two different host species, were used to investigate differences in their development in the blood and virulence in the experimentally infected canaries. Simultaneously, 258 kb of the parasite genome was screened for genetic differences using parasite mRNA and compared between experimental groups.

Results

The two isolates showed differences in development and caused mortality as well as effects on the blood parameters of their hosts. Although previous studies using single genes have shown very limited within lineage genetic diversity in the European population of SGS1, 226 SNPs were found across 322 genes, which separated the two experimental groups with a total of 23 SNPs that were fixed in either of the experimental groups. Moreover, genetic variation was found within each experimental group, hinting that each avian malaria infection harbours standing genetic variation that might be selected during each individual infection episode.

Conclusion

These results highlight extensive genetic variation within the SGS1 population that is transferred into individual infections, thus adding to the complexity of the infection dynamics seen in these host–parasite interactions. Simultaneously, the results open up the possibility of understanding how genetic variation within the parasite populations is linked to the commonly observed differences in infection outcomes, both in experimental settings and in the wild.

Graphical Abstract
Evaluating trends in damage to attractive targeted sugar baits (ATSBs) deployed during the second year of a two-year Phase III trial in Western Zambia
Authors: Kyomuhangi Irene , Yukich Joshua , Saili Kochelani , Orange Erica , Masuzyo Mundia H. , Mwenya Mwansa , Mambo Patricia , Hamainza Busiku , Wagman Joe , Miller John , Chanda Javan , Silumbe Kafula , Littrell Megan , Eisele Thomas P. , Ashton Ruth A.
Published: August 2024

Background

Attractive Targeted Sugar Baits (ATSBs) are a proposed new vector control tool for malaria that contain sugar and an ingestion toxicant, and are designed to attract and kill sugar-feeding mosquitoes. During a two-arm cluster randomized Phase III trial conducted in Zambia to test the efficacy of ATSB stations on malaria incidence, ATSB stations deployed on eligible household structures within intervention clusters were routinely monitored to ensure their good physical condition and high coverage. This study investigates trends in prevalence and rate of damage to ATSB stations during year 2 of the two-year trial.

Methods

The analysis was conducted using monitoring data collected in year 2, which included types of damage observed, location, and date of removal and/or replacement of ATSB stations. The study evaluated temporal trends in the prevalence of overall damage and different damage types among 68,299 ATSB stations deployed. A profile of all ATSB stations installed on each structure was constructed, and spatial analyses conducted on overall damage and different damage types observed on 18,890 structures. Mixed effects regression analyses were conducted to investigate drivers of damage to ATSB stations on these structures.

Results

Prevalence of overall damage and different damage types was temporally and spatially heterogeneous. Among damaged ATSB stations observed during monitoring, tears and mold had the highest prevalences on average, with tears maintaining above 50.0% prevalence through most of the monitoring period, while mold prevalence increased steadily during the first few months, peaking in February. Overall, 45.6% of structures had at least one damaged ATSB station, however this varied spatially across the trial site. Both structure characteristics and environmental factors significantly impacted the odds and rate of damage to ATSB stations on structures, including: ATSB stations’ level of protection from rainfall and sunshine; roof and wall material of the structure; night-time temperature; rainfall; enhanced vegetation index, and land cover.

Conclusion

Damage to ATSB stations in this setting was common and was temporally and spatially heterogeneous. This has implications on operational feasibility, sustainability, and cost of future deployment. Further research is required to understand the mechanisms of damage, and to minimize prevalence and rate of damage to ATSB stations.
Inclusion of people with disabilities in Chilean health policy: a policy analysis
Authors: Rodríguez Gatta Danae , Gutiérrez Monclus Pamela , Wilbur Jane , Hanefeld Johanna , Banks Lena Morgon , Kuper Hannah
Published: August 2024

Background

Around 18% of the population in Chile has disabilities. Evidence shows that this population has greater healthcare needs, yet they face barriers to accessing healthcare due to health system failures. This paper aims to assess the inclusion of people with disabilities in health policy documents and to explore the perceptions of key national stakeholders regarding the policy context, policy processes, and actors involved.

Methods

A policy content analysis was conducted of 12 health policy documents using the EquiFrame framework, adapted to assess disability inclusion. Documents were reviewed and rated on their quality of commitment against 21 core concepts of human rights in the framework. Key national stakeholders (n = 15) were interviewed, and data were thematically analysed under the Walt and Gilson Policy Analysis Triangle, using NVivo R1.

Results

Core human rights concepts of disability were mentioned at least once in nearly all health policy documents (92%). However, 50% had poor policy commitments for disability. Across policies, Prevention of health conditions was the main human rights concept reflected, while Privacy of information was the least referenced concept. Participants described a fragmented disability movement and health policy, related to a dominant biomedical model of disability. It appeared that disability was not prioritized in the health policy agenda, due to ineffective mainstreaming of disability by the Government and the limited influence and engagement of civil society in policy processes. Moreover, the limited existing policy framework on disability inclusion is not being implemented effectively. This implementation gap was attributed to lack of financing, leadership, and human resources, coupled with low monitoring of disability inclusion.

Conclusions

Improvements are needed in both the development and implementation of disability-inclusive health policies in Chile, to support the achievement of the right to healthcare for people with disabilities and ensuring that the health system truly “leaves no one behind”.
Montane evergreen forest deforestation for banana plantations decreased soil organic carbon and total nitrogen stores to alarming levels
Authors: Magalhães Tarquinio Mateus , Cossa Edna Rita Bernardo , Nhanombe Hunilcia Esperança , Mugabe Amélia David Muchanga
Published: August 2024

Forest conversion to agricultural land has been shown to deplete soil organic carbon (SOC) and soil total nitrogen (STN) stocks. However, research on how soil properties respond to forest conversion to shifting cultivation has produced conflicting results. The conflicting findings suggest that the agricultural system may influence the response of SOC and STN to forest conversion to agriculture, depending on the presence of vegetative cover throughout the year. Due to the unique characteristics of montane evergreen forests (MEF) and banana plantations (BP), SOC and STN response to MEF conversion to BP may differ from existing models. Nevertheless, research on how soil properties are affected by MEF conversion to BP is scarce globally. In order to fill this research gap, the goal of this study was to evaluate how much deforestation for BP affects SOC, STN, and soil quality by analysing these soil parameters in MEF and BP fields down to 1-m depth, using standard profile-based procedures. Contrary to the specified hypothesis that SOC and STN losses would be restricted to the upper 20-cm soil layer, SOC losses were extended to the 40-cm depth layer and STN losses to the 60-cm depth layer. The soils lost 18.56 Mg ha – 1 (37%) of SOC from the upper 20 cm and 33.15 Mg ha – 1 (37%) from the upper 40 cm, following MEF conversion to BP. In terms of STN, the upper 20, 40, and 60 cm lost 2.98 (43%), 6.62 (47%), and 8.30 Mg ha – 1 (44%), respectively. Following MEF conversion to BP, the SOC stratification ratio decreased by 49%, implying a decline in soil quality. Massive exportation of nutrients, reduced C inputs due to complete removal of the arboreal component and crop residues, the erodibility of the soils on the study area’s steep hillslopes, and the potential for banana plantations to increase throughfall kinetic energy, and splash erosion through canopy dripping are thought to be the leading causes of SOC and STN losses. More research is needed to identify the extent to which each cause influences SOC and STN losses.
How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature
Authors: Fleischmann-Struzek Carolin , Joost Franka E. A. , Pletz Mathias W. , Weiß Björn , Paul Nicolas , Ely E. Wesley , Reinhart Konrad , Rose Norman
Published: August 2024

Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.
MST1R-targeted therapy in the battle against gallbladder cancer
Authors: Wang Wei , Huang Chao , Zhang Li , Yu Liqin , Liu Yangming , Wang Puxiongzhi , Xia Rongmu
Published: August 2024

Background

Gallbladder cancer (GBC) is characterized by high mortality rate. Our study sought therapeutic candidates for GBC.

Results

Bioinformatics analysis identified significant upregulation of MST1R in GBC. In vitro experiments demonstrated that the MST1R inhibitor MGCD-265 effectively restrained GBC cell proliferation at lower concentrations. Additionally, it induced cycle arrest and apoptosis in GBC cells in a dose-dependent manner. Mouse models exhibited that MGCD-265 treatment significantly diminished the proliferative capacity of GBC-SD cells. Transcriptomics sequencing revealed significant transcriptome alterations, with 200 transcripts upregulated and 883 downregulated. KEGG and GO analyses highlighted enrichment in processes like cell adhesion and pathways such as protein digestion and absorption. Downstream genes analysis identified JMJD6 upregulation post-MGCD-265 treatment. In vivo experiments confirmed that combining MGCD-265 with the JMJD6 inhibitor SKLB325 enhanced the anticancer effect against GBC.

Conclusion

Overall, targeting MST1R and its downstream genes, particularly combining MGCD-265 with SKLB325, holds promise as a therapeutic strategy for GBC.
Ketamine-assisted buprenorphine initiation: a pilot case series
Authors: Grande Lucinda A. , Hutch Tom , Jack Keira , Mironov Wendy , Iwuoha Jessica , Muy-Rivera Martin , Grillo Jacob , Martin Stephen A. , Herring Andrew
Published: August 2024

Background

Many people with opioid use disorder who stand to benefit from buprenorphine treatment are unwilling to initiate it due to experience with or fear of both spontaneous and buprenorphine-precipitated opioid withdrawal (BPOW). An effective means of minimizing withdrawal symptoms would reduce patient apprehensiveness, lowering the barrier to buprenorphine initiation. Ketamine, approved by the FDA as a dissociative anesthetic, completely resolved BPOW in case reports when infused at a sub-anesthetic dose range in which dissociative symptoms are common. However, most patients attempt buprenorphine initiation in the outpatient setting where altered mental status is undesirable. We explored the potential of short-term use of ketamine, self-administered sublingually at a lower, sub-dissociative dose to assist ambulatory patients undergoing transition to buprenorphine from fentanyl and methadone.

Methods

Patients prescribed ketamine were either (1) seeking transition to buprenorphine from illicit fentanyl and highly apprehensive of BPOW or (2) undergoing transition to buprenorphine from illicit fentanyl or methadone and experiencing BPOW. We prescribed 4–8 doses of sublingual ketamine 16 mg (each dose bioequivalent to 3–6% of an anesthetic dose), monitored patients daily or near-daily, and adjusted buprenorphine and ketamine dosing based on patient response and prescriber experience.

Results

Over a period of 14 months, 37 patients were prescribed ketamine. Buprenorphine initiation was completed by 16 patients, representing 43% of the 37 patients prescribed ketamine, and 67% of the 24 who reported trying it. Of the last 12 patients who completed buprenorphine initiation, 11 (92%) achieved 30-day retention in treatment. Most of the patients who tried ketamine reported reduction or elimination of spontaneous opioid withdrawal symptoms. Some patients reported avoidance of severe BPOW when used prophylactically or as treatment of established BPOW. We developed a ketamine protocol that allowed four of the last patients to complete buprenorphine initiation over four days reporting only mild withdrawal symptoms. Two patients described cognitive changes from ketamine at a dose that exceeded the effective dose range for the other patients.

Conclusions

Ketamine at a sub-dissociative dose allowed completion of buprenorphine initiation in the outpatient setting in the majority of patients who reported trying it. Further research is warranted to confirm these results and develop reliable protocols for a range of treatment settings.
In what ways do AI techniques propel decision-making amidst volatility? Annotated bibliography perspectives
Authors: Zambrano Manzur Bryan N. , Espinoza Bazán Fabián A. , Novoa-Hernández Pavel , Cruz Corona Carlos
Published: August 2024

This research presents a systematic review and approximation, from 2018 to 2023, of how Artificial Intelligence can support decision-making processes when business managers have to resolve between multiple alternatives for the development of new businesses using Agile Frameworks; and as well, will be addressed from the genesis concepts such as VUCA, Agile Mindset, Infinite Game Theory, Agile Frameworks, Innovation, Artificial Intelligence among others with the aim of identifying research gaps in the decision-making process under changing environments. Most of the analyzed studies are focused on Infinity Games theory to better understand innovation processes linked from early stages to deployment phases of products. Furthermore, this paper analyzes AI techniques for decision-making under volatile circumstances and raises 5 research questions that from a logical and chronological perspective in development are resolved during the research. It is important to highlight that AI-related solutions are typically used to make informed decisions; however, few studies adopt AI to support the decision-making process in unstable environments.
Exploring drivers of self-treatment with antibiotics in three agricultural communities of northern Tanzania
Authors: Loosli Kathrin , Nasuwa Fortunata , Melubo Matayo , Mnzava Kunda , Matthews Louise , Mshana Stephen E. , Mmbaga Blandina T. , Muwonge Adrian , Davis Alicia , Lembo Tiziana
Published: August 2024

Background

Antimicrobial resistance (AMR) poses a significant global health threat, particularly in low- and middle-income countries (LMICs). Self-treatment with antibiotics, the practice of using antibiotics without professional guidance, is often considered an important contributor to the emergence and spread of AMR.

Method

This study investigated the drivers of self-treatment in three common types of agricultural communities in northern Tanzania. The research employed a comprehensive array of methods, including cross-sectional surveys (n = 790), interviews (n = 30) and observations (n = 178) targeting both antibiotic (human and animal) providers and users (patients and farmers). Qualitative interview data were analysed using a coding and association matrix, while descriptive analyses were performed on survey and observation data.

Results

Self-treatment with antibiotics was highly prevalent in all communities. Between 41.0% (self-reported) and 60.3% (observed) of human antibiotics were obtained without a prescription and we observed that veterinary antibiotics were regularly purchased in retail shops without referral by a professional. Structural deficiencies in the healthcare system drove this practice: limited access to healthcare facilities, medication stockouts and prolonged waiting times were identified as key factors. The absence of safety nets like insurance schemes further contributed to self-medication. Retail shops offered a convenient and cost-effective alternative when antibiotics were inaccessible or unaffordable. Notably, informal networks comprising treatment vendors, friends or neighbours, as well as personal experiences played a crucial role in guiding individuals in their self-treatment decisions by providing advice on treatment choice and modalities.

Conclusions

Addressing self-treatment requires a multi-faceted approach. Improving the availability and accessibility of antibiotics, enhancing healthcare services and involving retail vendors in antibiotic stewardship are essential. Structural issues like access to diagnostics and medicines must be tackled, alongside reducing barriers and incentivising individuals to use professional healthcare services. Training retail vendors to sell specific first-line antibiotics over the counter with guidance on appropriate usage should be considered. Such bottom-up interventions will enable sustainable promotion of responsible antibiotic use, mitigating AMR emergence and securing a healthier future for all.
Prokaryotic-virus-encoded auxiliary metabolic genes throughout the global oceans
Authors: Tian Funing , Wainaina James M. , Howard-Varona Cristina , Domínguez-Huerta Guillermo , Bolduc Benjamin , Gazitúa Maria Consuelo , Smith Garrett , Gittrich Marissa R. , Zablocki Olivier , Cronin Dylan R. , Eveillard Damien , Hallam Steven J. , Sullivan Matthew B.
Published: August 2024

Background

Prokaryotic microbes have impacted marine biogeochemical cycles for billions of years. Viruses also impact these cycles, through lysis, horizontal gene transfer, and encoding and expressing genes that contribute to metabolic reprogramming of prokaryotic cells. While this impact is difficult to quantify in nature, we hypothesized that it can be examined by surveying virus-encoded auxiliary metabolic genes (AMGs) and assessing their ecological context.

Results

We systematically developed a global ocean AMG catalog by integrating previously described and newly identified AMGs and then placed this catalog into ecological and metabolic contexts relevant to ocean biogeochemistry. From 7.6 terabases of Tara Oceans paired prokaryote- and virus-enriched metagenomic sequence data, we increased known ocean virus populations to 579,904 (up 16%). From these virus populations, we then conservatively identified 86,913 AMGs that grouped into 22,779 sequence-based gene clusters, 7248 (~ 32%) of which were not previously reported. Using our catalog and modeled data from mock communities, we estimate that ~ 19% of ocean virus populations carry at least one AMG. To understand AMGs in their metabolic context, we identified 340 metabolic pathways encoded by ocean microbes and showed that AMGs map to 128 of them. Furthermore, we identified metabolic “hot spots” targeted by virus AMGs, including nine pathways where most steps (≥ 0.75) were AMG-targeted (involved in carbohydrate, amino acid, fatty acid, and nucleotide metabolism), as well as other pathways where virus-encoded AMGs outnumbered cellular homologs (involved in lipid A phosphates, phosphatidylethanolamine, creatine biosynthesis, phosphoribosylamine-glycine ligase, and carbamoyl-phosphate synthase pathways).

Conclusions

Together, this systematically curated, global ocean AMG catalog and analyses provide a valuable resource and foundational observations to understand the role of viruses in modulating global ocean metabolisms and their biogeochemical implications.
Advancing the art of mosquito control: the journey of the sterile insect technique against Aedes aegypti in Cuba
Authors: Gato René , Menéndez Zulema , Rodríguez Misladys , Gutiérrez-Bugallo Gladys , del Carmen Marquetti María
Published: August 2024

Background

Aedes aegypti, the primary vector of dengue, chikungunya, and Zika viruses, poses a significant public health threat worldwide. Traditional control methods using insecticides are increasingly challenged by resistance and environmental concerns. The sterile insect technique (SIT) offers an eco-friendly alternative that has been successfully applied to other insect pests. This article aims to briefly review Ae. aegypti management in Cuba, highlighting the accomplishments, challenges, and future directions of the SIT.

Main body

Here we provide a brief summary of the extensive history of Ae. aegypti control efforts in Cuba. After a successful eradication campaign in the 1980s, a resurgence of dengue cases has been observed in recent years, suggesting that traditional control methods may have limited effectiveness under current conditions. In response, Cuba initiated a phased approach to develop and evaluate the feasibility of SIT for Ae. aegypti control, starting in 2008. Initial research focused on Ae. aegypti mating behavior and sterilization methods, followed by successful laboratory and semi-field trials that demonstrated population suppression. The first open-field trial in 2020 confirmed the efficacy of the SIT in reducing Ae. aegypti populations under real-world conditions. Currently, the research is in a phase involving a cluster-randomized superiority-controlled trial. This planned trial will compare the standard vector control program with the same program augmented by the SIT, aiming to assess the impact of the SIT on dengue incidence as the primary outcome. Implementing robust epidemiological trials to evaluate the effectiveness of the SIT is complex due to potential spillover effects from mosquito and human movement across study areas. Additionally, conducting the SIT requires significant development and operational investments. Despite these challenges, the ongoing Cuban trial holds promise for establishing the SIT as an effective and sustainable tool for Ae. aegypti control and for reducing the burden of mosquito-borne diseases.

Conclusions

The phased evaluation conducted in Cuba confirms the efficacy of the SIT against Ae. aegypti, highlighting its potential for sustainable mosquito-borne disease management. The effective implementation of multi-site trials will be crucial in providing evidence of the potential of the sterile insect technique as part of a strategy to reduce the incidence of arboviral diseases.

Graphical Abstract
The state of foresight in small and medium enterprises: literature review and research agenda
Authors: Dörr Ulrike-Sabine , Schönhofer Gerhard , Schwarz Jan Oliver
Published: August 2024

Small and medium-sized enterprises (SMEs) are the backbone of many economies. In today's world of VUCA (Volatility, Uncertainty, Complexity, Ambiguity), SMEs face diverse challenges to survive and stay competitive. SMEs must prepare themselves for these challenges by practicing foresight. However, foresight, and especially corporate foresight, has been conceptualized and researched in the context of large corporations. Applying foresight in SMEs is therefore complicated by the question of how to implement foresight in the context of SMEs given their specific requirements and limitations. This article provides an overview on the literature on the application of foresight in SMEs is, along with a summary of the extent to which SMEs conduct foresight from an organizational and individual perspective. Besides offering a compendium on the state of foresight in SMEs, a research agenda is formulated, incorporating the idea of a toolbox tailored to SMEs based on existing approaches and prior works.
Enhancing point cloud registration with transformer: cultural heritage protection of the Terracotta Warriors
Authors: Wang Yong , Zhou Pengbo , Geng Guohua , An Li , Zhou Mingquan
Published: August 2024

Point cloud registration technology, by precisely aligning repair components with the original artifacts, can accurately record the geometric shape of cultural heritage objects and generate three-dimensional models, thereby providing reliable data support for the digital preservation, virtual exhibition, and restoration of cultural relics. However, traditional point cloud registration methods face challenges when dealing with cultural heritage data, including complex morphological and structural variations, sparsity and irregularity, and cross-dataset generalization. To address these challenges, this paper introduces an innovative method called Enhancing Point Cloud Registration with Transformer (EPCRT). Firstly, we utilize local geometric perception for positional encoding and combine it with a dynamic adjustment mechanism based on local density information and geometric angle encoding, enhancing the flexibility and adaptability of positional encoding to better characterize the complex local morphology and structural variations of artifacts. Additionally, we introduce a convolutional-Transformer hybrid module to facilitate interactive learning of artifact point cloud features, effectively achieving local–global feature fusion and enhancing detail capture capabilities, thus effectively handling the sparsity and irregularity of artifact point cloud data. We conduct extensive evaluations on the 3DMatch, ModelNet, KITTI, and MVP-RG datasets, and validate our method on the Terracotta Warriors cultural heritage dataset. The results demonstrate that our method has significant performance advantages in handling the complexity of morphological and structural variations, sparsity and irregularity of relic data, and cross-dataset generalization.
Cartographies of warfare in the Indian subcontinent: Contextualizing archaeological and historical analysis through big data approaches
Authors: Smith Monica L. , Newton Connor
Published: August 2024

Some of the most notable human behavioral palimpsests result from warfare and its durable traces in the form of defensive architecture and strategic infrastructure. For premodern periods, this architecture is often understudied at the large scale, resulting in a lack of appreciation for the enormity of the costs and impacts of military spending over the course of human history. In this article, we compare the information gleaned from the study of the fortified cities of the Early Historic period of the Indian subcontinent (c. 3rd century BCE to 4th century CE) with the precolonial medieval era (9-17th centuries CE). Utilizing in-depth archaeological and historical studies along with local sightings and citizen-science blogs to create a comprehensive data set and map series in a “big-data” approach that makes use of heterogeneous data sets and presence-absence criteria, we discuss how the architecture of warfare shifted from an emphasis on urban defense in the Early Historic period to an emphasis on territorial offense and defense in the medieval period. Many medieval fortifications are known from only local reports and have minimal identifying information but can still be studied in the aggregate using a least-shared denominator approach to quantification and mapping.
Expectations of and perceived need for civil war in the USA: findings from a 2023 nationally representative survey
Authors: Wintemute Garen J. , Li Yueju , Velasquez Bradley , Crawford Andrew , Reeping Paul M. , Tomsich Elizabeth A.
Published: August 2024

Background

Surveys have found concerningly high levels of agreement that the United States will experience civil war soon. This study assesses variation in expectation of and perceived need for civil war with respondent sociopolitical characteristics, beliefs, firearm ownership, and willingness to engage in political violence.

Methods

Findings are from Wave 2 of a nationally representative annual longitudinal survey of members of the Ipsos KnowledgePanel, conducted May 18–June 8, 2023. All respondents to 2022’s Wave 1 who remained in KnowledgePanel were invited to participate. Outcomes are expressed as weighted proportions and adjusted prevalence differences, with p-values adjusted for the false discovery rate and reported as q-values.

Results

The completion rate was 84.2%; there were 9385 respondents. After weighting, half the sample was female (50.7%, 95% CI 49.4%, 52.1%); the weighted mean (± standard deviation) age was 48.5 (25.9) years. Approximately 1 respondent in 20 (5.7%, 95% CI 5.1%, 6.4%) agreed strongly or very strongly that “in the next few years, there will be civil war in the United States.” About 1 in 25 (3.8%, 95% CI 3.2%, 4.4%), and nearly 40% (38.4%, 95% CI 32.3%, 44.5%) of those who strongly or very strongly agreed that civil war was coming, also agreed strongly or very strongly that “the United States needs a civil war to set things right.” Expectation of and perceived need for civil war were higher among subsets of respondents who in Wave 1 were more willing than others to commit political violence, including MAGA Republicans, persons in strong agreement with racist beliefs or statements of the potential need for violence to effect social change, persons who strongly approved of specified extreme right-wing political organizations and movements, firearm owners who purchased firearms in 2020 or later, and firearm owners who carried firearms in public all or nearly all the time.

Conclusions

In 2023, the expectation that civil war was likely and the belief that it was needed were uncommon but were higher among subsets of the population that had previously been associated with greater willingness to commit political violence. These findings can help guide prevention efforts.
It is challenging to reproduce both anatomical and functional aspects of anterolateral reconstruction: postoperative 3D-CT analysis of the femoral tunnel position
Authors: Ryu Dong Jin , Kim Seoyeong , Kim Minji , Kim Joo Hwan , Kim Won Jae , Lim Dohyung , Wang Joon Ho
Published: August 2024

Background

This study aimed to evaluate the femoral tunnel position and fiber length of the anterolateral ligament (ALL) reconstruction compared with the natural anatomy of the ALL. We also evaluated whether the femoral tunnel position would affect residual pivot shift.

Methods

This study was a retrospective review of 55 knees that underwent ALL reconstruction considering the anatomical and functional aspects, during primary anterior cruciate ligament (ACL) reconstruction in the presence of a high-grade pivot shift or revisional ACL reconstruction. We determined the position of the femoral tunnel and the length of graft using a three-dimensional (3D)-computed tomography (CT) model after ALL reconstruction. We also measured graft excursion during surgery and examined pivot shift 2 years after surgery. We conducted a subgroup analysis of femoral tunnel position, fiber length, isometricity, and residual pivot shift depending on whether the tunnel was anterior or posterior to the lateral epicondyle (LE). We also performed a subgroup analysis depending on whether the ACL reconstruction was primary or revisional.

Results

The mean femoral tunnel position was 2.04 mm posterior and 14.5 mm proximal from the center of the LE. The mean lengths of the anterior and posterior fibers were 66.6 and 63.4 mm, respectively. The femoral tunnel was positioned more proximally than the anatomical position, and both anterior and posterior ALL fibers were longer than the natural anatomy. The anteroposterior femoral tunnel position was significantly correlated with anterior (p = 0.045) and posterior (p = 0.037) fiber excursion. In the subgroup analysis, there was no significant difference in the residual pivot shift between the posterior and anterior tunnel positions. However, there were significant differences for proximal position (p < 0.001) and fiber length (p = 0.006). There was no significant difference between primary and revisional ACL regarding femoral tunnel position and fiber lengths.

Conclusion

It is challenging to reproduce both anatomical and functional aspects of ALL reconstruction in both primary and revision ACL reconstruction. Especially for functional reconstruction, the femoral tunnel tended to be positioned more proximally than the anatomical position. However, the femoral tunnel position did not affect functional clinical outcomes at the 2-year follow-up.

Level of evidence

Level IV Case series.
Hemodynamic tolerability and efficacy of hemodialysis modalities in critically ill patients
Authors: Bandi Varun Kumar , Shekar Manikantan , Elumalai Ramprasad , Matcha Jayakumar
Published: August 2024

Introduction

Acute kidney injury (AKI) is frequently seen in critically ill patients and is associated with high mortality and morbidity. However, the optimal dialysis modality in such patients remains controversial. We examined the hemodynamic tolerability of hemodialysis modalities in critically ill individuals with AKI.

Methodology

Critically ill patients with AKI who underwent Continuous Renal Replacement Therapy (CRRT), Sustained Low-Efficiency Diafiltration (SLEDD-f), or Sustained Low-Efficiency Dialysis (SLED) dialysis were included in the study. In-hospital mortality, number of dialysis sessions, number of sessions terminated pre-maturely, change in blood pressure during dialysis, and hemodynamic instability during dialysis sessions were noted.

Results

A total of 264 patients were included, of which 78 received Continuous Renal Replacement Therapy (CRRT), 62 received Sustained Low-Efficiency Diafiltration (SLEDD-f), and 124 received Sustained Low-Efficiency Dialysis (SLED), with a total of 682 sessions among 264 patients. The commonest cause for AKI was septic shock (32.6%, n=43). All CRRT and SLEDD-f sessions were delivered without anticoagulation, and SLED was delivered without anticoagulation in 88.7% of sessions. There was a significant decrease in mean arterial pressure in CRRT compared to other modalities, with higher mortality. However, patients undergoing CRRT were more sicker. There was no significant difference between SLEDD-f and SLED in terms of outcomes.

Conclusion

SLEDD-f and SLED have good hemodynamic tolerability compared to CRRT. There was no significant difference in hemodynamic disturbances between SLEDD-f and SLED despite a higher proportion of patients on SLEDD-f being more critical.
A review of HSV pathogenesis, vaccine development, and advanced applications
Authors: Bai Lan , Xu Jiuzhi , Zeng Linghui , Zhang Long , Zhou Fangfang
Published: August 2024

Herpes simplex virus (HSV), an epidemic human pathogen threatening global public health, gains notoriety for its complex pathogenesis that encompasses lytic infection of mucosal cells, latent infection within neurons, and periodic reactivation. This intricate interplay, coupled with HSV's sophisticated immune evasion strategies, gives rise to various diseases, including genital lesions, neonatal encephalitis, and cancer. Despite more than 70 years of relentless research, an effective preventive or therapeutic vaccine against HSV has yet to emerge, primarily due to the limited understanding of virus-host interactions, which in turn impedes the identification of effective vaccine targets. However, HSV's unique pathological features, including its substantial genetic load capacity, high replicability, transmissibility, and neurotropism, render it a promising candidate for various applications, spanning oncolytic virotherapy, gene and immune therapies, and even as an imaging tracer in neuroscience. In this review, we comprehensively update recent breakthroughs in HSV pathogenesis and immune evasion, critically summarize the progress made in vaccine candidate development, and discuss the multifaceted applications of HSV as a biological tool. Importantly, we highlight both success and challenges, emphasizing the critical need for intensified research into HSV, with the aim of providing deeper insights that can not only advance HSV treatment strategies but also broaden its application horizons.