bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling farmers’ perceptions: a citizen science and machine learning approach to exploring drivers in the adequacy and fairness of water systems
Authors: Plakandaras Vasilios , Khadim Fahad Khan , Kazana Vassiliki , Anagnostou Emmanouil , Bagtzoglou Amvrossios C
Published: December 2024

Agricultural production sustains a large part of the population in the Great South area (sub-Saharan Africa, South America and South Asia), relying heavily on rainfed agriculture and partly on reservoir-based irrigation schemes. This study evaluates the effects of citizen science approaches in shaping the farmers’ perceptions towards adequacy of the quantity of the provided water and the fairness of the irrigation distribution system in the area, using as a case study a project implemented in the Upper Blue Nile (UBN) region of Ethiopia in two irrigated communities. Harnessing the analytical power of machine learning models in extracting patterns from data, the informational content of social surveys coupled with hydrological data for the survey region from a calibrated MODFLOW-NWT groundwater (GW) model, we draw inferences on the importance of socioeconomic rather than hydrological variables as drivers in agricultural decisions about crop selection and planting period, underscoring those factors as potential criteria in drawing successful agricultural policies for crop yield optimization in the Great South area. This study extends the existing literature towards understanding the interplay between people and water under a qualitative framework with distinct policy implications.
An optimized phishing detection model using hybrid feature selection and a fine-tuned narrow neural network with dynamic jaya optimization to overcome cyberthreats
Authors: Diviya M , Subramanian M , Gopala Krishnan D
Published: December 2024

The frequency of phishing assaults threatens the occurrence of online transactions. Criminals engaged in phishing utilize misleading strategies, such as fake URLs, to obtain sensitive information from consumers through media such as e-mails and texts. More efficient phishing detection techniques that use classifiers combining hybrid approaches of feature selection techniques and deep learning must be developed to handle attacks. The proposed work provides a unique method for improving phishing detection that combines a hybrid feature selection strategy with a fine-tuned narrow neural network (FTNN) and Dynamic Jaya optimization algorithm. The model works in two phases: a hybrid feature selection algorithm works for filtering the salient features and a fine-tuned narrow neural network architecture with and without optimization is suggested for classifying phishing and legitimate urls. The process starts by choosing a subset of 20 features from a total of 48 attributes. The model specifically uses chi-square and Kruskal–Wallis statistical feature ranking algorithms. The FTNN with Dynamic Jaya optimization performs best when large datasets are used for feature selection. The results demonstrate the superior performance of the proposed hybrid feature selection technique along with the Dynamic Jaya optimized FTNN architecture. It outperforms conventional methods that rely on all the features, resulting in higher accuracy than existing models. A higher accuracy of 97.5% has been achieved with the integration of hybrid feature selection with FTNN, compared to other traditional methods. This research provides a practical and desirable solution for enhancing hybrid feature selection along with a fine-tuned narrow neural network (optimized with Dynamic Jaya) in phishing detection. Hence, this work proposes an innovative hybrid feature selection approach, coupled with a fine-tuned neural network with enhanced recognition performance by the Dynamic Jaya algorithm, to present an efficient, accurate, and scalable identification of phishing compared to traditional methods. These innovations underscore the novelty of feature selection, light neural network, and optimization that in total enhances performance and applicability in tackling phishing.
Dynamic Deep Learning Based Super-Resolution For The Shallow Water Equations
Authors: Witte Maximilian , Lapolli Fabricio Rodrigues , Freese Philip , Götschel Sebastian , Ruprecht Daniel , Korn Peter , Kadow Christopher
Published: December 2024

Correctly capturing the transition to turbulence in a barotropic instability requires fine spatial resolution. To reduce computational cost, we propose a dynamic super-resolution approach where a transient simulation on a coarse meshis frequently corrected using a U-net-type neural network. For the nonlinear shallow water equations, we demonstrate that a simulation with the ICON-O ocean model with a 20 km resolution plus dynamic super-resolution trained on a 2.5 km resolution achieves discretization errorscomparable to a simulation with 10 km resolution. The neural network, originally developed for image-based super-resolution in post-processing, is trained to compute the difference between solutions on both meshes and is used to correct the coarsemesh solution every 12 h. We show that the ML-corrected coarse solution correctly maintains a balanced flow and captures the transition to turbulence in line with the higher resolution simulation. After a 8 d simulation, the L2-error of the corrected run issimilar to a simulation run on the finer mesh. While mass is conserved in the corrected runs, we observe some spurious generation of kinetic energy.
A bioluminescent reporter bioassay for in-process assessment of chimeric antigen receptor lentiviral vector potency
Authors: Gilden Julia K , Stecha Pete , Hartnett Jim , Cong Mei
Published: December 2024

Background

Chimeric antigen receptor (CAR)–T-cell therapy is a breakthrough in the field of cancer immunotherapy, wherein T cells are genetically modified to recognize and attack cancer cells. Delivery of the CAR gene is a critical step in this therapy and is usually achieved by transducing patient T cells with a lentiviral vector (LV). Because the LV is an essential component of CAR-T manufacturing, there is a need for simple bioassays that reflect the mechanism of action (MOA) of the LV and can measure LV potency with accuracy and specificity. Common methods for LV quantification may overestimate functional titer and lack a functional readout of LV MOA.

Methods

We developed a bioluminescent reporter bioassay using Jurkat T cells stably expressing a luciferase reporter under the control of an nuclear factor of activated T cells (NFAT) response element and tested its suitability for measuring LV potency.

Results

Jurkat reporter cells can be transduced with CAR LV and combined with target cells, yielding a luminescent signal that is dependent on the identity and potency of the LV used. Bioluminescence was highly correlated with CAR expression. The assay is stability indicating and suitable for use in drug development and quality control settings.

Conclusions

We have developed a simple bioassay for potency testing of CAR LV. The bioassay represents a significant improvement over other approaches to LV quantification because it reflects the MOA of the LV and selectively detects fully functional viral particles, making it ideal for inclusion in a matrix of in-process quality control assays for CAR LV.
CParty: hierarchically constrained partition function of RNA pseudoknots
Authors: Gray Mateo , Trinity Luke , Stege Ulrike , Ponty Yann , Will Sebastian , Jabbari Hosna
Published: December 2024

Motivation

Biologically relevant RNA secondary structures are routinely predicted by efficient dynamic programming algorithms that minimize their free energy. Starting from such algorithms, one can devise partition function algorithms, which enable stochastic perspectives on RNA structure ensembles. As the most prominent example, McCaskill’s partition function algorithm is derived from pseudoknot-free energy minimization. While this algorithm became hugely successful for the analysis of pseudoknot-free RNA structure ensembles, as of yet there exists only one pseudoknotted partition function implementation, which covers only simple pseudoknots and comes with a borderline-prohibitive complexity of O(n5) in the RNA length n.

Results

Here, we develop a partition function algorithm corresponding to the hierarchical pseudoknot prediction of HFold, which performs exact optimization in a realistic pseudoknot energy model. In consequence, our algorithm CParty carries over HFold’s advantages over classical pseudoknot prediction in characterizing the Boltzmann ensemble at equilibrium. Given an RNA sequence S and a pseudoknot-free structure G, CParty computes the partition function over all possibly pseudoknotted density-2 structures G∪G′ of S that extend the fixed G by a disjoint pseudoknot-free structure G′. Thus, CParty follows the common hypothesis of hierarchical pseudoknot formation, where pseudoknots form as tertiary contacts only after a first pseudoknot-free “core” G and we call the computed partition function hierarchically constrained (by G). Like HFold, the dynamic programming algorithm CParty is very efficient, achieving the low complexity of the pseudoknot-free algorithm, i.e. cubic time and quadratic space. Finally, by computing pseudoknotted ensemble energies, we unveil kinetics features of a therapeutic target in SARS-CoV-2.

Availability and implementation

CParty is available at https://github.com/HosnaJabbari/CParty.
Ribosomal protein L36-mediated selective loading of microRNA-4432 into extracellular vesicles contributes to perivascular cell dysfunction in venous malformations
Authors: Chen Gao-Hong , Ren Jian-Gang , Xia Hou-Fu , Zhang He-Jing , Wang Kui-Ming , Zhang Lin-Zhou , Chen Gang
Published: December 2024

Background

Venous malformations (VMs), predominantly arising from activating mutations of TIE2 in endothelial cells (ECs), are characterized by dilated and tortuous vessels with a paucity of perivascular cells (PCs). The mechanisms of interaction between mutant ECs and PCs remain largely elusive.

Objectives

To investigate the characteristics of extracellular vesicles (EVs) from VM ECs, especially the microRNAs (miRNAs) carried and their roles in crosstalk between ECs and PCs in VM pathogenesis.

Methods

miRNA profiles of human umbilical vein endothelial cells overexpressing TIE2L914F (L914F cells) and TIE2WT [wildtype (WT) cells], along with their EVs, were analysed by RNA sequencing. In vitro studies using umbilical cord stem cells (UCSCs) were done to carry out functional assays of VM EVs and their enriched miRNA-4432 (miR-4432). miRNA pulldown and RNA interference techniques were used to identify the sorting regulator of miR-4432 into VM EVs.

Results

RNA secretion was upregulated in L914F EVs vs. WT EVs. miRNA sequencing revealed a distinct profile of L914F EVs vs. L914F cells, WT cells and WT EVs, identifying miR-4432 as being preferentially encapsulated in EVs from L914F cells. Functional assays demonstrated that VM EVs and EV-carried miR-4432 inhibited the differentiation, adhesion and proliferation of UCSCs. Furthermore, ribosomal protein L36 (RPL36) was identified as an RNA binding protein and sorting regulator of miR-4432 during the EV secretion process in L914F cells.

Conclusions

This study, for the first time, identified an interaction between VM ECs and PCs via EVs, and offers valuable data on the miRNA profiles of VM ECs and normal ECs, along with their EVs. Our findings suggest that the RPL36-mediated selective loading of miR-4432 into EVs may contribute to the aberrant PC coverage in VMs, providing novel insights into VM pathogenesis and potential treatment strategies.
Partial or focal brachytherapy for prostate cancer: a systematic review and meta-analysis
Authors: Gutiérrez-Valencia Enrique , Navarro-Domenech Inmaculada , Zhou Kailee , Barcelona Marc , Fazelzad Rouhi , Ramotar Matthew , Sanchez Irving , Ruiz Victor , Weersink Robert , Glicksman Rachel , Helou Joelle , Berlin Alejandro , Chung Peter , Chow Ronald , Raman Srinivas
Published: December 2024

Objectives

Recent advances in image-guided brachytherapy have allowed for treatment volume reduction in the treatment of prostate cancer, with the aim to optimize disease control and reduce toxicities. This systematic review reports on the efficacy and safety of focal brachytherapy for treatment of patients with localized prostate cancer.

Methods

Medline, Embase, Web of Science, and Cochrane were searched from inception to July 2023. Studies were included if they reported on focal brachytherapy, and described either dosimetry or clinical outcomes in the monotherapy or salvage setting. Meta-analysis was conducted to estimate biochemical control (BC) at 12-60 months. The review protocol was registered on PROSPERO (CRD42022320921).

Results

Twenty-six studies reporting on 1492 patients were included in this review. Fourteen studies reported on monotherapy, 10 on salvage, and two on boost. The majority of studies used MRI and/or biopsy or PET for target identification, and MRI fusion and transrectal ultrasound (TRUS) for image guidance technique. BC for monotherapy was 97% (95% CI: 86%-99%) at 24 months and 82% (95% CI: 65%-92%) at 60 months. BC for salvage was 67% (95% CI: 62%-72%) at 24 months and 35% (95% CI: 17%-58%) at 60 months. Low rates of toxicity were reported across studies.

Conclusions

Focal brachytherapy has promising efficacy and safety profiles. Future studies may compare focal brachytherapy to whole-gland treatments, to investigate relative efficacy and safety.

Advances in knowledge

In well-selected patients, partial or focal brachytherapy represents an evidence-based option with acceptable BC rates and a favourable toxicity profile.
ESG, Externalities, and the Limits of the Business Judgment Rule: TEPCO Derivative Suit on Fukushima Nuclear Accident and the Expansion of Caremark
Authors: Goto Gen
Published: December 2024

While there is a general agreement that corporate directors may consider stakeholder interests beyond legal requirements, opinions diverge on whether they are obligated to do so. The traditional approach emphasizes directors’ primary responsibility to the company and shareholders, granting them broad discretion in deciding how to improve the firm value. However, recent cases in Japan and the United States suggest a trend toward limiting this discretion. Tokyo District Court’s TEPCO decision found directors liable for inadequate tsunami preparedness that led to the meltdown of Fukushima 1st Nuclear Power Plant, while Delaware courts denied motions to dismiss by defendant directors for their breach of the Caremark duty of oversight, seemingly expanding its scope to cases where there were no specific violations of laws or regulations. This expansion, which may promote sustainability, potentially conflicts with the business judgment rule—a fundamental principle encouraging optimal risk-taking and value maximization. The combination of limited business judgment protection and extensive personal liability could severely discourage director risk-taking, potentially harming corporate and economic growth. This article examines when business judgment rule limitations are appropriate for businesses with significant negative externality risks. It analyzes the TEPCO decision and Caremark duty expansion, exploring various justifications and their implications. The article argues that oversight duties should be contextualized based on risk types and externalities. Given ESG’s broad scope—from climate change to human rights—careful unpacking of the concept is necessary to appropriately address serious externalities while avoiding excessive duty expansion’s negative consequences.
Design and Analytical Evaluation of Novel Cardiac Troponin Assays Targeting Multiple Forms of the Cardiac Troponin I–Cardiac Troponin T–Troponin C Complex and Fragmentation Forms
Authors: Li Ling , Liu Yuqing , Katrukha Ivan A , Zhang Litao , Shu Xin , Xu Ao , Yang Juan , Wu Yu , Jing Yisha , Wang Hui , Ni Tongxin , Schulz Karen , Bereznikova Anastasia V , Katrukha Alexey G , Apple Fred S , Zhang Yi , Zhang Zhenlu
Published: December 2024

Background

Current studies suggest that cardiac troponin (cTn) forms in the circulation may vary in different clinical scenarios. Our aim was to design a combination of cTn assays specific to the main cTn forms and to evaluate their analytical performance.

Methods

We developed immunoassays specific for measuring (1) long-cTnT cTnI-cTnT-TnC (ITC) ternary complex, with cTnT in long form without cleavage at the C-terminal amino acids residue 189–223, designated “long-cTnT ITC complex assay;” (2) both the long-cTnT ITC complex plus short-cTnT ITC complex, designated “hs-total ITC complex assay;” (3) the central part of cTnT of both the long-cTnT ITC complex and free cTnT, designated “hs-cTnT assay.” Sex-specific 99th percentile upper reference limits (URLs) were determined. High-sensitivity performance was assessed by examining the imprecision and detectable results above limit of detection (LoD) in the healthy population.

Results

Both complex immunoassays exhibited excellent analytical sensitivity, precision, and specificity. The 99th percentile URLs were as follows: long-cTnT ITC complex: male 0.90 ng/L, female 0.87 ng/L; hs-total ITC complex: male 16.15 ng/L, female 10.08 ng/L; hs-cTnT: male 15.57 ng/L, female 14.28 ng/L. The total imprecision at or below the sex-specific 99th percentile URLs was <5% for all assays. The hs-total ITC complex and the hs-cTnT assays showed >50% of measurable concentrations above the LoD. However, <20% were measurable for the long-cTnT ITC complex assay.

Conclusions

The cTn assays detected concentrations of major cTn forms in the circulation with high sensitivity, precision, and specificity, supporting their use for monitoring cTn complex and fragmentation forms during myocardial injuries.
Characterization of Cardiac Troponin Fragment Composition Reveals Potential for Differentiating Etiologies of Myocardial Injury
Authors: Li Ling , Liu Yuqing , Katrukha Ivan A , Zhang Litao , Shu Xin , Xu Ao , Yang Juan , Wu Yu , Jing Yisha , Wang Hui , Ni Tongxin , Schulz Karen , Bereznikova Anastasia V , Katrukha Alexey G , Apple Fred S , Zhang Yi , Zhang Zhenlu
Published: December 2024

Background

Increased cardiac troponin (cTn) concentrations occur in acute myocardial injury and chronic diseases. Characterization of cTn composition in the circulation may assist in differentiating etiologies of myocardial injury. Our goal was to study cTn composition and kinetics in patients following type 1 myocardial infraction (T1MI), cardiac procedures, and chronic heart diseases to establish the relationship between cTn composition and clinical diagnosis.

Methods

Plasma samples were collected from 201 patients with T1MI, 78 undergoing cardiac surgeries, and 218 with chronic cardiomyopathy or chronic heart failure. Major cTn forms in the circulation and their ratios were analyzed using cTn composition immunoassays, targeting (a) the long-cTnT cTnI–cTnT–TnC (ITC) ternary complex, short-cTnT ITC complex cleaved at amino acids residues 189–223 of cTnT, and the binary cTnI-TnC (IC) complex, and designated the “high-sensitivity (hs)-cTnI assay;” (b) the long-cTnT ITC complex, and designated the “long-cTnT ITC complex assay;” (c) the long-cTnT ITC complex and short-cTnT ITC complex, and designated the “hs-total ITC complex assay;” and (d) the central part of cTnT of both the long-cTnT ITC complex and free cTnT, and designated the “hs-cTnT assay.”

Results

Early-stage T1MI patients showed a high ratio of long-cTnT ITC complex to cTnI (long-cTnT ITC complex/cTnI, R1). Similarly, patients after acute cardiac surgery exhibited increased cTn concentrations with high R1, which decreased rapidly. In chronic disease, cTn composition exhibited stable and low R1 and high ratios of cTnT to cTnI (cTnT/cTnI, R3).

Conclusions

Kinetic differences in multiple cTn forms contribute to the differentiation between acute injury and chronic disease, with a high proportion of long-cTnT ITC complex implying occurrence of acute injury.
Connecting the dots: relationship between heart rate and overall dynamic body acceleration in free-ranging cattle
Authors: Niccolai L J , Devineau Olivier , Thiel Alexandra , Zimmermann Barbara , Evans L Alina
Published: December 2024

Monitoring physiological indicators including heart rate (HR) is crucial for managing animal welfare across diverse settings, from precision livestock farming to wildlife conservation. HR is a reliable indicator of energy expenditure and stress, yet the invasive nature of HR loggers limits their application in wild and free-ranging species. This study explores whether overall dynamic body acceleration (ODBA), measured with an external accelerometer, can serve as a less invasive proxy for HR. Using free-ranging cattle as a model species in Norway, we examined the relationship between ODBA and HR to assess how external accelerometry might indirectly reflect physiological states in settings that resemble wild conditions. Cattle provide an ideal model because they share some characteristics with wild herbivores, including exposure to diverse terrain and potential predation, whilst offering advantages for handling and sensor retrieval. Our findings showed that low ODBA values corresponded to static behaviours (e.g. standing, ruminating), where small movements caused HR spikes, whilst higher ODBA reflected dynamic activities (e.g. walking, foraging), with HR plateauing. This relationship suggests that ODBA can be used to approximate HR in environments where direct HR measurement is challenging. By using accelerometry to infer HR changes in free-ranging cattle, this study offers insights that could extend to wild species, offering a tool for conservationists to monitor and manage animal health and well-being less invasively.
Clinical Outcomes After First-Line Anti- Tumor-Necrosis-Factor Treatment of Patients With Inflammatory Bowel Disease—A Prospective Multicenter Cohort Study
Authors: Zhao Mirabella , Larsen Lone , Dige Anders , Poulsen Anja , Lo Bobby , Attauabi Mohamed , Ovesen Pernille Dige , Wewer Mads Damsgaard , Christiansen Dagmar , Hvas Christian Lodberg , Petersen Andreas Munk , Bendtsen Flemming , Seidelin Jakob , Burisch Johan
Published: December 2024

Background and Aims

Existing findings on outcomes of anti-tumor-necrosis-factor (TNF) therapy in patients with inflammatory bowel diseases (IBD) are largely based on retrospective studies. We aimed to investigate real-world outcomes of anti-TNF therapy and predictors thereof in a prospective IBD cohort.

Methods

In a Danish multicenter cohort of adult bio-naïve patients with IBD treated with anti-TNF, we assessed clinical response and remission to induction therapy using clinical disease activity scoring indices at Week 14. In patients who continued treatment beyond the induction period, we also assessed loss of response (LOR), drug withdrawal, and major IBD surgery during maintenance therapy.

Results

This study included 774 patients (706 infliximab, 68 adalimumab) followed for a median duration of 125 weeks Clinical response was achieved in 209/331 (67.4%) of ulcerative colitis (UC) and 125/197 (74.0%) of Crohn’s disease (CD) patients, while 143/331 (46.1%) UC and 81/197 (47.9%) CD patients achieved clinical remission. In 294 UC and 309 CD patients received maintenance therapy, while 86/294 (29.3%) UC and 78/309 (25.2%) CD patients experienced LOR. Active smoking and less severe disease activity predicted favorable outcomes in UC, while short disease duration, colonic disease, nonstricturing behavior, and concomitant immunomodulator therapy predicted favorable outcomes in CD.

Conclusions

Clinical response was achieved in 2 in 3 UC and 3 in 4 CD patients, meanwhile, one-third of UC and one-fourth of CD patients experienced LOR despite the short disease duration in this study. Several clinical features were associated with outcomes and may be useful predictors of anti-TNF treatment response.
Surgical management of traumatic tricuspid regurgitation: a case report
Authors: Buttiglione Gianpiero , Höfer Daniel , Hangler Herbert , Bonaros Nikolaos
Published: December 2024

Background

Traumatic tricuspid valve regurgitation is a rare condition related to blunt chest trauma. In the early phase, the patients may remain asymptomatic. Progressive tricuspid regurgitation leads to the development of symptoms thereafter. Progressive right ventricular dysfunction aggravates symptoms, and the diagnosis is made by subsequent echocardiography at a later time. The treatment is usually surgical, especially in younger patients.

Case summary

We describe a 30-year-old patient with traumatic tricuspid valve regurgitation after a motorcycle accident. No cardiac injury was detected at the moment of the collision, and the patient remained asymptomatic at the initial phase. Five years later, the patient was admitted to our hospital with symptoms of dyspnoea at exertion. Echocardiography demonstrated severe tricuspid valve regurgitation with right ventricle dilatation. Surgical tricuspid valve repair including ring annuloplasty and implantation of artificial chords via an endoscopic approach was performed. Surgery was complicated by impingement of the right coronary artery by one of the annuloplasty sutures, which was addressed by subsequent percutaneous coronary intervention.

Discussion

Traumatic tricuspid valve regurgitation requires careful evaluation. Transthoracic echocardiography should be recommended to exclude post-traumatic tricuspid regurgitation after major blunt chest trauma. Early diagnosis is important to avoid right ventricular failure. First-line surgical treatment consists of tricuspid repair by means of ring annuloplasty and implantation of artificial chords.
Efficacy of an Internet of Things-based system for cardiac rehabilitation monitoring: insights from the IntellIoT pivotal trial in heart failure patients
Authors: Marketou Maria E , Anastasiou Ioannis , Fourlis Alexis , Alevizaki Aphrodite , Kochiadakis George
Published: December 2024

Aims

Digital health solutions targeted to remote clinical monitoring are constantly gaining ground in cardiovascular care. However, evidence regarding their impact on cardiac rehabilitation efficiency in heart failure (HF) patients is relatively limited. In this study, conducted in the context of the IntellIoT project, we evaluated the effect of a purpose-designed Internet of Things (IoT)-based patient monitoring system on cardiac rehabilitation outcomes in a cohort of HF patients.

Methods and results

Nineteen clinically stable HF patients were enrolled in the study, which consisted of a 12-month standard-of-care run-in phase and a remote follow-up phase of equal duration, whereby an IoT-based e-health system was provided to study subjects. Device-derived data transmission was facilitated by a mobile phone application, coupled with a web-based platform accessible to study physicians. Study endpoints were (i) patient adherence rates to e-health system use and their associations to key clinical parameters, (ii) the degree of change in physical activity, and (iii) total time dedicated by physicians to enrolled patients’ care with and without the aid of the e-health system. Baseline-to-peak increase in daily step count was calculated at 23.34%. System use was associated with a decrease in time dedicated by physicians to enrolled patients’ care. A significant negative correlation was observed between age and progressive drop-in adherence rate to system use (r = −0.5722, P = 0.02).

Conclusion

Internet of Things-based healthcare constitutes a promising approach in HF patients’ rehabilitation, whereas elderly patients might constitute the population most likely to benefit. However, larger, randomized studies are required to confirm our findings.
The type of environment has a greater impact on the larval microbiota of Anopheles arabiensis than on the microbiota of their breeding water
Authors: Assentato Lorenzo , Nilsson Louise K J , Brunius Carl , Feltelius Vilhelm , Elleby Rasmus , Hopkins Richard J , Terenius Olle
Published: December 2024

Mosquito larvae of the genus Anopheles develop entirely in water, frequently visiting the surface for air. The aquatic environment plays a key role in shaping their microbiota, but the connection between environmental characteristics of breeding sites and larval microbiota remains underexplored. This study focuses on Anopheles arabiensis, which inhabits the surface microlayer (SML) of breeding sites, a zone with high particle density. We hypothesized that the SML could allow us to capture the diversity of the surrounding environment, and in turn its influence on the larval microbial communities. To test this, we collected A. arabiensis larvae and SML samples from various breeding sites categorized by environmental features. Our results confirm that breeding site characteristics are significant drivers of the bacterial species present in mosquito larvae. Additionally, we found that the larval micro-environment selectively shapes its microbiota, highlighting a dynamic interplay between environmental and internal factors. Interestingly, specific bacterial families were associated with the presence or absence of larvae in breeding sites, suggesting potential ecological roles. These findings expand our understanding of vector-mosquito microbiota, emphasizing the importance of breeding site features in shaping larval microbial communities and providing a foundation for future research on mosquito ecology and control strategies.
Proteomic identification of a Toxoplasma gondii sporozoite-specific antigen using HDAC3 inhibitor-treated tachyzoites as surrogate
Authors: Warschkau David , Klein Sandra , Schadt Ella , Doellinger Joerg , Schares Gereon , Seeber Frank
Published: December 2024

The apicomplexan parasite Toxoplasma gondii has a complex life cycle. Access to sexual stages and sporozoite-containing oocysts, essential for studying the parasite’s environmental transmission, is limited and requires animal experiments with cats. Thus, alternatives and resource-efficient methods are needed. Several molecular factors and transcriptional switches responsible for differentiation have been identified in recent years. In tachyzoites, drug-induced inhibition of the histone deacetylase HDAC3, or genetic depletion of transcription factors regulating HDAC3, leads to the expression of genes that are specific to sexual stages and oocysts. Here, we applied this concept and showed that the commercially available HDAC3 inhibitor apicidin could be used to identify the hitherto unknown antigen of the sporozoite-specific monoclonal antibody G1/19 in tachyzoites. Using mass spectrometry of immunoprecipitated G1/19 target protein from apicidin-treated cultures, we identified it as SporoSAG. In addition, for the much less abundant sporozoite-specific protein LEA860, apicidin treatment was still sufficient to induce a detectable protein level in immunofluorescence microscopy. We also discuss further applications and the limitations of this approach. This allows to overcome issues with the paucity of material of sexual stages and oocysts from T. gondii to some extent without the need for cat-derived material.
New insights toward the design of an effective trapping method for Coraebus undatus F. (Coleoptera: Buprestidae)
Authors: Mannu Roberto , López Sergio , Quero Carmen , Olivieri Maurizio , Ruiu Pino Angelo , Lentini Andrea
Published: December 2024

Coraebus undatus has emerged as a significant threat to the health and productivity of Quercus suber in the Mediterranean region, as its attacks result in a depreciation of commercialized cork planks, leading to severe economic losses. The development of an effective monitoring methodology is essential for the optimal implementation of management strategies as the level of C. undatus infestation can only be assessed after cork debarking. Hence, we conducted a series of studies to assess the efficacy of trap type, color, and size, as well as lure type, for trapping C. undatus. Field trials were conducted in 2020 and 2023 in various infested cork oak stands in Sardinia (Italy). The results demonstrated that the four trapping systems tested (i.e. cross-vane interception traps, prism traps, panel traps, and plastic films) were effective in intercepting C. undatus females. The number of females found in purple cross-vane traps in 2020 was consistently higher than that of other colored traps (i.e. black, green) regardless of the lure tested (cork oak green leaf volatiles or a mixture of three longhorn beetle pheromones). However, data from 2023 field trials showed that the attractiveness of unbaited purple prism traps was higher than that of traps releasing host volatiles. Our observations also revealed that the trapping surface had a significant effect on the number of insects intercepted when testing panel traps. Among the trapping methods we tested, unbaited sticky purple films attached to the cork oak trunk yielded the highest number of catches. Overall, this work contributes to the body of knowledge on the features influencing the efficiency of trapping C. undatus. Our results serve as a baseline for the development of an effective monitoring tool, which may be further improved for use in a mass trapping program.
A free lunch: microhaplotype discovery in an existing amplicon panel improves parentage assignment for the highly polymorphic Pacific oyster
Authors: Thompson Neil F , Sutherland Ben J G , Green Timothy J , Delomas Thomas A
Published: December 2024

Amplicon panels using genotyping by sequencing methods are now common, but have focused on characterizing SNP markers. We investigate how microhaplotype (MH) discovery within a recently developed Pacific oyster (Magallana gigas) amplicon panel could increase the statistical power for relationship assignment. Trios (offspring and two parents) from three populations in a newly established breeding program were genotyped on a 592 locus panel. After processing, 92% of retained amplicons contained polymorphic MH variants and 85% of monomorphic SNP markers contained MH variation. The increased allelic richness resulted in substantially improved power for relationship assignment with much lower estimated false positive rates. No substantive differences in assignment accuracy occurred between SNP and MH datasets, but using MHs increased the separation in log-likelihood values between true parents and highly related potential parents (aunts and uncles). A high number of Mendelian incompatibilities among trios were observed, likely due to null alleles. Further development of a MH panel, including removing loci with high rates of null alleles, would enable high-throughput genotyping by reducing panel size and therefore cost for Pacific oyster research and breeding programs.
Controlling the frequency dynamics of homing gene drives for intermediate outcomes
Authors: Camm Benjamin J , Fournier-Level Alexandre
Published: December 2024

Gene drives have enormous potential for solving biological issues by forcing the spread of desired alleles through populations. However, to safeguard from the potentially irreversible consequences on natural populations, gene drives with intermediate outcomes that neither fixate nor get removed from the population are of outstanding interest. To elucidate the conditions leading to intermediate gene drive outcomes, a stochastic, individual allele-focused gene drive model was developed to simulate the diffusion of a homing gene drive in a population. The frequencies of multiple alleles at a locus targeted by a gene drive were tracked under various scenarios. These explored the effect of gene drive conversion efficiency, strength and frequency of resistance alleles, dominance and strength of a fitness cost for the gene drive, and the level of inbreeding. Four outcomes were consistently observed: fixation, loss, temporary, and equilibrium. The latter 2 are defined by the frequency of the gene drive peaking then crashing or plateauing, respectively. No single variable determined the outcome of a drive. The difference between the conversion efficiency and resistance level, modeled quantitatively, differentiated the temporary and equilibrium outcomes. The frequency dynamics of the gene drive within outcomes varied extensively, with different variables driving these dynamics between outcomes. These simulation results highlight the possibility of fine-tuning gene drive outcomes and frequency dynamics. To that end, we provide a web application implementing our model, which will guide the safer design of gene drives able to achieve a range of controllable outcomes tailored to population management needs.
Tracing value from social determinant solutions
Authors: Nichols Len M , Waidman Timothy A , Clemans-Cope Lisa , Garrett Bowen , Taylor Kima
Published: December 2024

We develop and illustrate a framework to trace value from social determinants of health (SDOH) interventions across 4 dimensions: health, cost and quality, engagement, and equity. To provide context, we begin by estimating the societal value lost to premature deaths from homelessness and food insecurity, using recent longitudinal methods that offer greater precision. We then apply the value tracing framework to 2 example interventions: permanent supportive housing for chronically homeless people and medically tailored meals for dual eligibles. These examples are supported by a narrative review of relevant literature, highlighting evidence from high-quality studies of SDOH projects that often show a broader range of benefits to multiple stakeholders. Prior research frequently overlooks non-healthcare savings, concluding that interventions “don’t pay for themselves.” In contrast, our findings show that when all beneficiaries are considered, many SDOH interventions yield a net positive value. Recognizing the public good nature of SDOH interventions is essential for reaching accurate policy conclusions. This paper advocates for greater recognition and estimation of the multiple sources of value in payment policies and investment decisions. Additional SDOH interventions and practical examples for local coalitions are provided in appendices.
Intestinal Ultrasound Measures are Strongly Correlated With Small Bowel Endoscopic Lewis Score in Active Crohn’s Disease
Authors: Ukashi Offir , Lahat Adi , Ungar Bella , Veisman Ido , Levy Hadar , Sharif Kassem , Eidler Pinhas , Eliakim Rami , Kopylov Uri , Carter Dan , Ben-Horin Shomron , Albshesh Ahmad
Published: December 2024

Background

Small bowel video capsule endoscopy (SB-VCE) assesses mucosal inflammation in Crohn’s disease (CD), while intestinal ultrasound (IUS) examines transmural involvement. We aimed to correlate SB-VCE with IUS in evaluating active CD and monitoring treatment response over time.

Methods

Patients with active SB-CD who initiated biologics were prospectively followed with fecal calprotectin (FC), SB-VCE, and IUS at baseline and after 14 and 52 weeks. The Lewis score (LS), Limberg index (LI), and terminal ileum bowel wall thickness (TI-BWT) were documented, and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was retrospectively calculated. Biochemical, endoscopic, and ultrasonographic remission were defined as FC < 150 μg/g, LS < 135, and LI < 2 + TI-BWT ≤ 3 mm, respectively. A therapeutic response for each index was defined as a 25% reduction compared to baseline.

Results

Seventy-one patients were included (median age: 30 years [23-43], 49.3% male). The median interval between SB-VCE and IUS was 3 days (0-25). Initially, the LS strongly correlated with TI-BWT (r = 0.647, P < .001), LI (r = 0.597, P < .001), and IBUS-SAS (r = 0.647, P < .001), but these correlations weakened over time (TI-BWT: r = 0.344, P = .002; LI: r = 0.471, P = .001; IBUS-SAS: r = 0.236, P = .122). Moderate agreement was found between ultrasonographic and endoscopic treatment responses (LS and TI-BWT: K = 0.51, P = .015; LS and LI: K = 0.44, P = .063), with fair agreement for remission (K = 0.27, P = .006). TI-BWT best cutoffs for mild (LS ≥ 135) and moderate-to-severe (LS ≥ 790) inflammation were 2.25 mm and 3.6 mm, respectively

Conclusions

IUS measures are strongly correlated with VCE-inflammatory LS in active CD and may provide an assessment of endoscopic response and remission over time.
Analyzing and mitigating the risks of patient harm during operating room to intensive care unit patient handoffs
Authors: Martins Nara Regina Spall , Martinez Edson Zangiacomi , Simões Cláudia Marquez , Barach Paul Randall , Carmona Maria José Carvalho
Published: December 2024

Patients continue to suffer from preventable harm and uneven quality outcomes. Reliable clinical outcomes depend on the quality of robust administrative systems and reliable support processes. Critically ill patient handoffs from the operating room (OR) to the intensive care unit (ICU) are known to be high-risk events. We describe a novel perspective on how risk factors associated with the process of patient handoff communication between the OR and the ICU can lead to flawed communication, degraded team awareness, medical errors, and increased patient harm. Data were collected from two semi-structured focus groups using a five-step risk management approach at a tertiary hospital in São Paulo, Brazil. We conducted a failure modes and effects analysis (FMEA) with multidisciplinary healthcare providers consisting of attending physicians, anesthesiologists, nurses, and physiotherapists involved in patient handoffs. We analyzed the results using a similitude analysis to evaluate the effectiveness of implementing this novel risk management approach. We identified the handoffs risks associated with patients, staff, institution, and potential financial risks. The FMEA identified 12 process failures and 36 causes that generated 12 consequences and pointed to robust needed preventive measures to mitigate handoff risks. The clinical teams reported that this approach allowed them to see the process more completely as a whole not only in their narrow silos, thus understanding the enablers and difficulties of the other team members and how this understanding can shed light on their mental models, actions, and the process reliability. Teams identified key steps in the OR to ICU handoff process that are prone to the highest hazards to patients, the hospital, and staff, and are currently targeted for process improvement. Evidence-driven recommendations intended for reducing the risks associated with patient handoffs are presented. Implementing a dynamic risk management, interdisciplinary approach was used to redesign the OR to ICU patient handoff approach around the patient’s and clinician’s needs. The risk management program helped healthcare providers identify handoff steps, highlighting risky handoff process failures, making it possible to identify actionable failures, consequences, and define preventative action plans for mitigating the risks to improve the quality and safety of patient handoffs.
Antimicrobial resistance–attributable mortality: a patient-level analysis
Authors: Baltas Ioannis , Rawson Timothy Miles , Houston Hamish , Grandjean Louis , Pollara Gabriele
Published: December 2024

Background

The impact of antimicrobial resistance (AMR) on death at the patient level is challenging to estimate. We aimed to characterize AMR-attributable deaths in a large UK teaching hospital.

Methods

This retrospective study investigated all deceased patients in 2022. Records of participants were independently reviewed by two investigators for cases of AMR-attributable deaths using a newly proposed patient-level definition.

Results

In total, 758 patients met inclusion criteria. Infection was the underlying cause of death for 11.7% (89/758) and was implicated in the pathway that led to death in 41.1% (357/758) of participants. In total, 4.2% (32/758) of all deaths were AMR-attributable. Median time from index sample collection to death was 4.5 days (IQR 2–10.5 days). The majority of AMR-attributable deaths (56.3%, 18/32) were associated with intrinsic resistance mechanisms, primarily by Enterococcus faecium (20.7%), Enterobacterales carrying repressed chromosomal ampicillinase Cs (AmpCs) (14.7%) and Pseudomonas aeruginosa (11.8%), whereas a minority (43.7%, 14/32) had acquired resistance mechanisms, primarily derepressed chromosomal AmpCs (11.8%) and ESBLs (8.8%). The median time to effective treatment was 32 h 15 min (no difference between subgroups). Only 62.5% (20/32) of AMR-attributable deaths had infection recorded on the death certificate. AMR was not recorded as a cause of death in any of the patients.

Conclusions

Infection and AMR were important causes of death in our cohort, yet they were significantly underreported during death certification. In a low-incidence setting for AMR, pathogen-antimicrobial mismatch due to intrinsic resistance was an equally important contributor to AMR-attributable mortality as acquired resistance mechanisms.
Assessment of anti-MRSA activity of auranofin and florfenicol combination: a PK/PD analysis
Authors: Li Jian-Guo , Zhang Chuan-Jian , Liang Liu-Yan , Lu Ting-Yin , Zhong Long-Gen , Zhong Wei-Cheng , Niu Chao-Yan , Sun Jian , Liao Xiao-Ping , Zhou Yu-Feng
Published: December 2024

Aims

Methicillin-resistant Staphylococcus aureus (MRSA) is an important zoonotic pathogen with multidrug-resistant phenotypes increasingly prevalent in both human and veterinary clinics. This study evaluated the potential of auranofin (AF) as an antibiotic adjuvant to enhance the anti-MRSA activity of florfenicol (FFC) and established a pharmacokinetic/pharmacodynamic (PK/PD) model to compare the efficacy of FFC alone or in combination with AF against MRSA.

Methods and results

We observed an increased susceptibility and significant synergistic effects of MRSA to FFC in the presence of AF. The combination treatment of FFC and AF significantly inhibited MRSA biofilm formation and decreased the metabolic activity of mature biofilms. Importantly, AF fully restored the efficacy of FFC in both Galleria mellonella larvae and murine models. PK/PD studies demonstrated that the AUC24h/MIC targets required to achieve the bacteriostatic and bactericidal effects were significantly lower with the combination therapy compared to florfenicol monotherapy.

Conclusions

These results reveal the potential of AF as a novel adjuvant to improve the efficacy of FFC in treating MRSA invasive infections and provide valuable PK/PD insights for designing effective combination therapies.