bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐exchange neutrophil count, but not post‐hematocrit, predicts endogenous erythropoiesis in patients with sickle cell disease undergoing chronic red cell exchange
Authors: Yurtsever Nalan , Tong Nicholas , Geetha Saroja , Nandi Vijay , Shi Patricia A.
Published: October 2024

Background

With chronic transfusion in sickle cell disease (SCD), equipoise exists regarding whether increasing the post‐procedure hematocrit (Hct) suppresses endogenous erythropoiesis. Reticulocytosis predicts SCD morbidity and mortality, so this study's objective was to clarify the role of the post‐procedure Hct in suppressing reticulocytosis and to identify other potential red cell exchange (RCE) parameters predictive of reticulocytosis.

Study Design and Methods

This retrospective analysis of 17 patients who underwent chronic RCE at a single institution between 2014 and 2022 examined both standard red cell exchanges (SRCE) and exchanges preceded by isovolemic hemodilution (IVH‐RCE). Post‐procedure parameters with biologic plausibility to influence the subsequent procedure's absolute reticulocyte count (sPre‐ARC) were examined using regression modeling.

Results

Neither post‐hematocrit, nor post‐hemoglobin (Hb), nor ΔHb/day was associated with sPre‐ARC or the change in HbS% per day (ΔHbS%/day). Concurrent Hb was predictive for SRCE but not IVH‐RCE, where ARC trended lower than with SRCE. Male gender and post‐procedure neutrophil and white cell counts were predictors of sPre‐ARC, consistent with their associations with SCD morbidity and mortality. IVH‐RCE had a stronger correlation than standard RCE between pre‐Hct and neutrophil or white cell depletion.

Discussion

Although targeting a post‐procedure Hct maintains a higher subsequent pre‐procedure Hb and a lower sPre‐HbS%, it does not lead to sustained suppression of reticulocytosis as measured by the sPre‐ARC or the ΔHbS%/day. IVH‐RCE or the addition of hydroxyurea could be considered in those patients with high reticulocyte, white blood cell, or neutrophil counts.
Ex vivo comparison of full‐thickness biopsy techniques in the equine small intestine
Authors: Verhaar Nicole , Hammer Elisabeth , Reineking Wencke , Hewicker‐Trautwein Marion , Geburek Florian
Published: October 2024

Objective

To compare the practicability and tissue sample quality between different intestinal biopsy techniques.

Study design

Experimental, randomized ex vivo study.

Sample population

Small intestine of nine horses.

Methods

Four different biopsy techniques were evaluated in the aboral jejunum and the ileum within 1 h after euthanasia. One segment was used as control (C), and the applied techniques included an 8 mm biopsy punch (BP), transverse wedge resection (TW), longitudinal wedge resection with transverse closure (LW) and a longitudinal sample using Eppendorfer biopsy forceps (EF). Defects were closed using a single‐layer continuous Lembert pattern. Duration of the procedure, intestinal diameter, contamination, and bursting pressure were determined. The quality of the obtained tissue samples for histological assessment was evaluated using a semiquantitative score. The jejunal and ileal samples were analyzed separately.

Results

All biopsy procedures including defect closure were completed within 5 min, with shorter closure times for BP (p = .03). Minimal contamination could be noted in 1/8 TW and 2/8 LW cases, without significant differences between the groups. Longitudinal closure techniques (BP, EF) showed more constriction than transverse closures (TW, LW) (p < .05). Bursting pressure was >75 mmHg in all cases. Technique BP showed significantly lower biopsy quality scores (p = .009).

Conclusion

The tested biopsy techniques could all be applied effectively within a reasonable time frame, yet the biopsy punch was associated with significant artifacts and risk of missing mucosa.

Clinical significance

The findings provide insights into the possible advantages and limitations of the different techniques and alert the surgeon to potential issues with the quality of the tissue sample.
Immobilization of Cadmium Via Ureolytic Bacteria Isolated from Greywater Waste and Horse Faeces
Authors: Afandi Anis Amira , Basri Hazlami Fikri , Omoregie Armstrong Ighodalo , Mokhter Mohd Akmali , Hara Hirofumi , Ouahbi Tariq
Published: October 2024

With the constant growth of technology and pollution caused by urban expansion, heavy metal contamination has become an alarming concern. The performance of Microbial induced carbonate precipitation technology in immobilizing heavy metal has been demonstrated by several researchers. While various studies have successfully isolated ureolytic bacteria from a variety of sources, there are very limited studies that have focused on isolating them from local waste sources, specifically Greywater and Horse Faeces for MICP application, which benefits in terms of economical, sustainability, and efficiency for engineering purposes. The study aims to investigate the effect of urease-producing bacteria derived from Greywater and horse faeces on heavy metal immobilization. The methods include collecting waste samples, isolating and subculturing of ureolytic bacteria, testing the physiological characteristics of ureolytic bacteria, examining the tolerance test and evaluating heavy metal removal efficacy through Atomic Absorption Spectrophotometry (AAS) analysis, and last but not least, Scanning Electron Microscopy (SEM) and Energy-Dispersive X-ray (EDX) analyses of morphological and mineralogical properties of biominerals formed after heavy metal immobilization treatment. The study found that bacteria from Greywater were more effective at heavy metal immobilization than those from Horse Faeces. Additionally, AAS analysis indicates the greywater-derived bacteria from the residential area sample's exceptional competence in Cd2+ removal, with a significant 80.19% removal rate exceeding the horse faeces bacteria sample's removal rate of 65.26%. The morphological analysis confirmed the presence of heavy metal carbonate in treated heavy metal samples, as well as presenting insight into the effectiveness and application of local ureolytic bacteria's potential for heavy metal toxicity degradation.
Galerkin’s Method and Multivariate Newton’s Method for the Nonlinear Deformation of the Magneto-Electro-Elastic Bi-Layered Laminates
Authors: Mei-Feng Liu  , Siaw Ching Liew
Published: October 2024

In this paper, mathematical modelling for the large deformation of a magneto-electro-elastic rectangular bi-layered laminate with general boundary conditions is presented. Constitutive equations involving the magneto-electro-elastic (MEE) material properties are introduced, Maxwell equations accounts for the electric and magnetic effects are also utilized. First-order shear deformation theory (FSDT) considering the von Karman nonlinear strain is adopted, and the plain strain/stress assumption applicable for thin plate analysis is used. A rather compact set of governing equations related to kinematical variables, electric/magnetic potentials and the Airy stress function is obtained as a consequence of the preliminary condensation for the electro-magnetic state to the plate kinematics. Semi-analytic solution for a bi-layered BaTiO3-CoFe2O4 laminate with specified boundary conditions subjected to various external applied loads is performed. By employing the Bubnov-Galerkin method, the set of nonlinear partial differential equations is transformed to a set of third-order nonlinear algebraic equations for the static deformation due to applied load. Numerical results are carried out by using the multivariate Newton's method with respect to various volume fractions indicating the volume ratio between piezoelectric BaTiO3 layer and piezomagnetic CoFe2O4. From the result, the nonlinearity of the von Karman strain appears to enhance system rigidity as smaller deformations will be detected when external load is applied. Also, some other interesting results are obtained which could be useful to future analysis and design of multiphase composite plates.
Cd2+ Sequestration by Ureolytic Bacteria Isolated from Goat Faeces and Nursery Wastewater
Authors: Hamdan Muhammad Daniel , Basri Hazlami Fikri , Omoregie Armstrong Ighodalo , Mokhter Mohd Akmali , Iwamoto Koji , Ouahbi Tariq
Published: October 2024

As modern industrial production makes extensive use of heavy metals, a significant amount of sewage and solid wastes containing heavy metals are released into the environment. There is significant potential for bioremediation of multiple heavy metal contamination using biomineralization to immobilise the toxic metal. In this study, microbially induced carbonate precipitation (MICP) technology was used to treat Cd2+ contamination on plants, humans, and the environment. Ureolytic bacteria that collected from goat faeces and nursery wastewater were stimulated using enrichment technique. Next, physicochemical properties of the bacteria including urea agar base test, biomineralization test, conductivity & pH measurement test and optical density test were examined through enrichment subculturing of the bacteria. The morphological characterization of precipitate formed from both samples were analayzed by using scanning electron microscopy- energy dispersive x-ray diffraction method. Ureolytic bacteria of the goat faeces sample demonstrated greater tolerance to Cd2+ concentration compared to the nursery wastewater sample by obtaining a higher optical density values and larger amounts of precipitate produced by the goat faeces sample across all tested Cd2+ concentrations. As a result, from the atomic absorption spectrophotometry (AAS) analysis, the goat faeces sample showed higher efficiency in removing Cd2+ compared to the nursery wastewater sample, with a removal efficiency of 89.06% for the goat faeces sample and 77.75% for the nursery wastewater sample. Hence, this study confirmed that the interaction between ureolytic bacteria isolated from waste sources and heavy metal ions is vital for the overall effectiveness of heavy metal removal.
Electronegativity Effects on Conformational Stability Using Bent's Rule: From Simple Molecules to Acetylcholine
Authors: Rusydi Febdian
Published: October 2024

Hybridization and electronegativity are fundamental concepts in chemistry connected by Bent's rule. This rule explains many aspects of the structural chemistry and reactivity of organic and inorganic compounds. Over decades, the application of Bent's rule has expanded, demonstrating its wide-ranging utility in elucidating molecular stability due to the substitution of highly electronegative atoms. This study successfully leverages Bent's rule to explain conformational energy difference in acetylcholine case using density-functional calculations. We used butane (Group 2) and butanone (Group 3) families to model the head of ACh+ and substituted one of the carbons with highly electronegative atoms: B, C, N, and O. This enabled us to evaluate the effects of electronegativity, as well as the presence of carbonyl groups, on their conformational stability and s character. There were three highlighted results. First, our calculations result in the s character are consistent with Bent's rule. Second, the high conformational energy differences can be attributed to the changes of s character in C2–Z bond: linear in Group 2 and exponential in Group 3, indicating the strong contribution of the carbonyl group. Third, the key determining factor in ACh+ conformational stability is the carbonyl group, which also strongly contributes to the solute-solvent interactions. Therefore, our study can be further applied to other similar molecules, potentially leading to broader applications in chemistry, especially for understanding ACh+ stability for Alzheimer’s Disease treatment.
Crisis PR in the New Media Era: the Impact on the Reputation of Chinese New Energy Businesses
Authors: Lin Zhuoxin , Chen Yumin
Published: October 2024

The self-transformation of new media presents unprecedented challenges for crisis PR. In recent years, the rapid development of new energy vehicles in China has often led to widespread criticism when facing crisis Public Relations (PR) issues. This study takes Tesla, NIO, and Li Auto, three companies developing new energy vehicles in China. It compares their crisis PR strategies in the new media era, exploring their impact on corporate reputation. By collecting the quantity of cognitive and emotional assessments of positive, neutral, and negative nature, and calculating the conversion between evaluations of different natures, this research finds that incorrect response strategies lead to a decrease in both emotional and cognitive reputations, while successful response strategies primarily enhance cognitive reputation. Successful strategies may involve subjective proactive measures, characterized by swift or preemptive PR, positive emotional attitudes, and sustained responsiveness. This study provides empirical insights into understanding and addressing the challenges of crisis PR in the new media era, offering references for companies to formulate crisis management strategies.
Turán densities for daisies and hypercubes
Authors: Ellis David , Ivan Maria‐Romina , Leader Imre
Published: October 2024

An ‐daisy is an ‐uniform hypergraph consisting of the six ‐sets formed by taking the union of an ‐set with each of the 2‐sets of a disjoint 4‐set. Bollobás, Leader and Malvenuto, and also Bukh, conjectured that the Turán density of the ‐daisy tends to zero as . In this paper we disprove this conjecture. Adapting our construction, we are also able to disprove a folklore conjecture about Turán densities of hypercubes. For fixed and large , we show that the smallest set of vertices of the ‐dimensional hypercube that intersects every copy of has asymptotic density strictly below , for all . In fact, we show that this asymptotic density is at most , for some constant . As a consequence, we obtain similar bounds for the edge‐Turán densities of hypercubes. We also answer some related questions of Johnson and Talbot, and disprove a conjecture made by Bukh and by Griggs and Lu on poset densities.
Isometries of Lipschitz‐free Banach spaces
Authors: Cúth Marek , Doucha Michal , Titkos Tamás
Published: October 2024

We describe surjective linear isometries and linear isometry groups of a large class of Lipschitz‐free spaces that includes, for example, Lipschitz‐free spaces over any graph. We define the notion of a Lipschitz‐free rigid metric space whose Lipschitz‐free space only admits surjective linear isometries coming from surjective dilations (i.e., rescaled isometries) of the metric space itself. We show that this class of metric spaces is surprisingly rich and contains all 3‐connected graphs as well as geometric examples such as nonabelian Carnot groups with horizontally strictly convex norms. We prove that every metric space isometrically embeds into a Lipschitz‐free rigid space that has only three more points.
Impacts of time‐restricted feeding on middle‐aged and old mice with obesity
Authors: Yang Yueze , Liu Dexi
Published: October 2024

Time‐restricted feeding is known to ameliorate obesity in young mice. However, evaluation of its effect in old age is still lacking. The current work aims to investigate the effects of time‐restricted feeding on treating pre‐existing obesity in old animals. The study utilized middle‐aged and old high fat diet‐induced obese mice and subjected them to 8 h daily time‐restricted feeding. Aged obese mice did not lose fat mass but lost lean mass after 8 weeks of treatment. In addition, time‐restricted feeding reduced adiposity in brown adipose tissue, reversed excessive hepatic lipid accumulation, and improved glucose homeostasis in middle‐aged and old obese mice. Mechanistic studies show that these metabolic benefits were mediated by transcriptional downregulation of essential genes responsible for hepatic adipogenesis and adipose tissue chronic inflammation. These results demonstrate that time‐restricted feeding improves metabolic health and has beneficial effects in combating diet‐induced obesity in aged obese mice.

image

Key points

Contrary to in young obese mice, in old obese mice time‐restricted feeding did not significantly reduce body fat but decreased lean mass.

Time‐restricted feeding reduced adipose tissue inflammation, reversed fatty liver, and improved glucose homeostasis in aged mice with diet‐induced obesity.

Time‐restricted feeding is effective in improving metabolic homeostasis in aged mice, but less effective in terms of reducing obesity. Future studies should investigate the underlying mechanism of how ageing impaired intermittent fasting induced fat loss.
Coupled Thermo-Electric-Elastic Piezoelectric Vibration Energy Harvester With Axial Movement: Modeling, Verification, and Analysis
Authors: Zhang Huirong , Inman Daniel J. , Zhou Shengxi
Published: October 2024

In the field of rail transport and aerospace field, vibration energy harvesting is inevitably subjected to coupled excitations, including train wheel–track interaction induced friction heat and forced vibration, periodic thermal radiation, and vibration excitation. This paper investigates a coupled thermo-electric-elastic piezoelectric vibration energy harvester with axial movement under external heat flux and mechanical force load. The coupled forced vibration equation, coupled electric equation, and coupled thermoelastic heat conduction equation are derived and solved by Green's function theory. To analyze the effect of excitations on the response characteristics, the decoupled method is utilized to solve the coupled multi-field equations and obtain the displacement, electric, and temperature distribution closed-form solutions. The displacement coupling effect induced temperature distribution and the thermo-electric coupling effect triggered displacement are respectively decoupled and analyzed. The obtained closed-form temperature distribution and displacement solutions are verified by the finite element method. To further verify the obtained solutions, a numerical method is conducted by decoupling the coupled multi-field equations and comparing them with prior solutions. Additionally, the different height-to-length ratios, axially moving speeds, and external force load are analyzed in detail. The results indicate that the displacement, temperature distribution, and output voltage vary with external conditions due to the coupled multi-field effect. Overall, this work investigates the thermo-electric-elastic coupling effect on the axially moving piezoelectric energy harvesting, which is beneficial to promote theoretical investigations of the coupled multi-field energy harvesting system and accelerate the practical applications in the aerospace field.
Distribution of Flow Characteristics and Productivity Evaluation of Herringbone Wells in Bottom-Water Reservoirs
Authors: Liu Yuewu , Cui Chunxue , Zhou Zhijun , Zhang Guoqing , Ren Yangqi
Published: October 2024

With the characteristics of large drainage area and low drilling cost, the herringbone wells are becoming a significant way to boost the well production, improve the dynamic flow profile, delay the coning of bottom water, and enhance the development effect. Due to the complex flow characteristics of herringbone wells, result in a disparity between expected and actual production, therefore, it is crucial to investigate the productivity and flow characteristics of herringbone wells. In this paper, taking into account the interference between branch wellbores and perforations, the herringbone wells productivity model in bottom-water reservoirs is derived, the flow characteristics and the productivity sensitivity factors are analyzed. The results indicate that the transient flow time in reservoir is brief and that pressure changes increase with proximity to the wellbore, the productivity declines as the production time increases and subsequently tends to a certain value, reaching a quasi-steady-state. The per unit length radial inflow of wellbore decreases as the branch length, branch angle, and the number of branches increase, however, the rate of decrease slows down when exceeding three branches. The phase angle has a larger effect on production in high anisotropy reservoirs, and the production is the highest at 180 deg phase angle. When the perforation density rises above 16 shots/m, the production increasing trend slows down. This study provides significant guidance for practical application in the oil fields, including optimizing the shape of herringbone wells, allocating production in a rational manner, defining appropriate work systems, and improving oil recovery in bottom-water reservoirs.
Effect of Isobutanol/Gasoline Blends on the Performance and Emissions of an Otto Engine-Powered Vehicle Operating on a Driving Cycle
Authors: Herrera Correa Sergio Andres , Gallego Montoya Anderson , Lenis Rodas Yuhan Arley
Published: October 2024

This study experimentally investigates the performance and emissions of a typical vehicle in the Latin American automobile sector—specifically, a 1.6L spark ignition engine with port fuel injection (PFI) was used. The tests were performed using a Mustang MD150 chassis dynamometer under transient running conditions following the worldwide harmonized light test cycle (WLTC). Commercial gasoline (containing 10 vol% ethanol; E10) was blended with 10, 20, and 30 vol% of isobutanol. Results reveal that despite the reduction in the fuel lower heating value (LHV), adding the isobutanol B20 blend can improve the fuel economy by up to 6%. Similarly, when the alcohol content in the blend increased, the carbon monoxide (CO) and hydrocarbon (HC) emissions decreased by 10.5% and 10.2%, respectively. Furthermore, the B30 blend resulted in the lowest emissions but had the highest fuel consumption. Notably, these results were achieved without any adjustments to engine key components. Thus, the effects of isobutanol were consistent with the increase in octane and oxygenation of fuel blends.
A cross-linguistic review of citation tone production studies: Methodology and recommendations
Authors: Xu Chenzi , Zhang Cong
Published: October 2024

The study of citation tones, lexical tones produced in isolation, is one of the first steps towards understanding speech prosody in tone languages. However, methodologies for investigating citation tones vary significantly, often leading to limited comparability of tone inventories, both within and across languages. This paper presents a systematic review of research methods and practices in 136 citation tone studies on 129 tonal language varieties in China, including 99 studies published in Chinese, which are therefore not easily available to an international scientific readership. The review provides an overview of possible analytical decisions along the research pipeline, and unveils considerable variation in data collection, analysis, and reporting conventions, particularly in how f0, the primary acoustic correlate for tone, is operationalised and reported across studies. Key methodological issues are identified, including small sample sizes and inadequate transparency in communicating methodological decisions and procedure. This paper offers a clear road map for citation tone production research and proposes a range of recommendations on speaker sampling, experimental design, acoustic processing techniques, f0 analysis, and result reporting, with the goal of facilitating future tonal research and enhancing resources for underrepresented tonal varieties.
Assessing the Use of Recommended Practices in Adapted Physical Activity/Education Experiential-Learning Programs
Authors: Case Layne , Yun Joonkoo , MacDonald Megan , Hatfield Bridget E. , Logan Samuel W.
Published: October 2024

This study investigated the use of recommended practices in university-based experiential learning associated with adapted physical activity and education (APA/E) undergraduate courses. Participants (N = 165) were instructors of APA/E courses with an experiential-learning component and/or professionals involved in APA/E experiential-learning programs at their university. Participants completed an online questionnaire designed to describe program characteristics and evaluate the use of two sets of practices, including those recommended for involving students and people with disabilities. Findings highlight low proportions of the use of practices recommended for people with disabilities and indicate that significantly more practices recommended for students were implemented (Z = −10.45, p < .001). Findings from this study have several implications for evaluation and intervention in APA/E experiential learning, such as including the disability community in planning and designing programming to benefit both students and people with disabilities. Instructors should aim to increase their implementation of practices recommended for involving people with disabilities.
Gender Gap for Accelerometry-Based Physical Activity Across Different Age Groups in 5 Brazilian Cohort Studies
Authors: Ricardo Luiza I.C. , Wendt Andrea , Tornquist Debora , Gonçalves Helen , Wehrmeister Fernando , da Silva Bruna Gonçalves C. , Tovo-Rodrigues Luciana , Santos Iná , Barros Aluisio , Matijasevich Alicia , Hallal Pedro C. , Domingues Marlos , Ekelund Ulf , Bielemann Renata M. , Crochemore-Silva Inácio
Published: October 2024

Objectives: This study aims to evaluate the gender inequalities in accelerometer-based physical activity (PA) across different age groups using data from 5 Pelotas (Brazil) cohorts. Methods: The data come from 4 birth cohort studies, covering all live births in the urban area of Pelotas for each respective year (1982, 1993, 2004, and 2015), and the Como vai? cohort study focusing on 60 years and above. Raw accelerometry data were collected on the nondominant wrist using GENEActive/ActiGraph devices and processed with the GGIR package. Overall PA was calculated at ages 1, 2, 4, 6, 11, 15, 18, 23, 30, and 60+ years, while moderate to vigorous PA was calculated from 6 years onward. Absolute (difference) and relative (ratio) gender inequalities were calculated and intersectionality between gender and wealth was also evaluated. Results: The sample sizes per cohort ranged from 965 to 3462 participants. The mean absolute gender gap was 19.3 minutes (95% confidence interval, 12.7–25.9), with the widest gap at 18 years (32.9 min; 95% confidence interval, 30.1–35.7) for moderate to vigorous PA. The highest relative inequality was found in older adults (ratio 2.0; 95% confidence interval, 1.92–2.08). Our intersectionality results showed that the poorest men being the most active group, accumulating around 60 minutes more moderate to vigorous PA per day compared with the wealthiest women at age 18. Conclusions: Men were more physically active than women in all ages evaluated. PA gender inequalities start at an early age and intensify in transition periods of life. Relative inequalities were marked among older adults.
La reconnaissance du sport pour handicapés physiques par l’État français: gestion des effets inattendus d’une scission fédérale (1963–1977)
Authors: Ferez Sylvain , Ruffié Sébastien
Published: October 2024

Après sa création en 1963, la Fédération Sportive des Handicapés Physiques de France (FSHPF) engage un timide mouvement de structuration régionale, avec la mise en place d’un Comité Régional Lyonnais-Forez-Dauphiné-Savoie (CR-LFDS) – à côté de celui d’Ⓘle-de-France – en 1965. À partir de 1968, le renforcement des liens avec le département d’État français à la Jeunesse et aux sports contribue à accentuer ce mouvement. La FSHPF, renommée FFSHP en 1968, obtient finalement une délégation de pouvoirs de ce département le 20 juin 1972. Cet article revient sur les conditions de cette reconnaissance accélérée par l’État. A partir du croisement des archives du département d’État à la Jeunesse et aux sports et des archives fédérales, il montre ce que, paradoxalement, cette reconnaissance doit à la crise qui conduit, début 1972, à une scission du mouvement en deux fédérations rivales (la FFSHP et la FFOHP, créé à l’initiative du président du CR-LFDS).
How Racial Tasking Leads to Inequitable Financial Remuneration Among Power-5 College Football Coaches
Authors: Corr Chris , Macaulay Charles D.T. , Atwater Christopher , Sellars Nicole
Published: October 2024

While occupying a significant number of coaching positions in Power-5 college football, Black coaches are routinely overlooked as head coach or coordinator candidates. Although Black Power-5 football coaches generate significant value for their respective teams, such stagnation within the promotion and hiring of Black assistant coaches raises concerns about whether Black coaches receive equitable compensation for the value they generate. Utilizing Ray’s theory of racialized organizations, this study examined the race and salary of Power-5 football coaches to determine whether Black and White coaches receive equitable compensation. Results reveal that while Black coaches create inordinate value in recruiting prospective athletes, compensation among White Power-5 football coaches is exponentially greater than their Black counterparts. The economic value of Black and White stakeholders (e.g., coaches and athletes) to the college football enterprise is also discussed.
Molecular diagnostics in cerebrospinal fluid for the diagnosis of central nervous system infections
Authors: Olie Sabine E. , Andersen Christian Ø. , van de Beek Diederik , Brouwer Matthijs C.
Published: October 2024

Central nervous system (CNS) infections can be caused by various pathogens, including bacteria, viruses, fungi, and parasites. Molecular diagnostic methods are pivotal for identifying the different causative pathogens of these infections in clinical settings. The efficacy and specificity of these methods can vary per pathogen involved, and in a substantial part of patients, no pathogen is identified in the cerebrospinal fluid (CSF). Over recent decades, various molecular methodologies have been developed and applied to patients with CNS infections. This review provides an overview of the accuracy of nucleic acid amplification methods in CSF for a diverse range of pathogens, examines the potential value of multiplex PCR panels, and explores the broad-range bacterial and fungal PCR/sequencing panels. In addition, it evaluates innovative molecular approaches to enhance the diagnosis of CNS infections.
Harnessing the host response for precision infectious disease diagnosis
Authors: Woodhouse E. Wilbur , McClain Micah T. , Woods Christopher W.
Published: October 2024

Detection of the presence of infection and its etiology must be accurate and timely to facilitate appropriate antimicrobial use. Diagnostic strategies that rely solely on pathogen detection often are insufficient due to poor test characteristics, inability to differentiate colonization from infection, or protracted delay to result. Understanding the human response across different pathogens on a clinical and molecular level can provide more accurate, timely, and useful answers, especially in critical illness and diagnostic uncertainty. Improvements in understanding the human immune response including genomics, protein analysis, gene expression, and cellular morphology have led to rapid innovation of new host response-based diagnostic tests. This review describes the limitations of pathogen-focused technology and the benefits of examining the breadth of immune response to diagnose infection. It then explores biomarkers that have been studied for this purpose and scrutinizes the performance of host-based multianalyte testing. Currently cleared diagnostics and those in late-stage development are described in depth, with a focus on the purpose of testing and its utility for clinicians. Finally, it concludes by examining opportunities for further host response-derived diagnostic innovation.
Artemisinin-resistant malaria
Authors: White N. J. , Chotivanich K.
Published: October 2024

The artemisinin antimalarials are the cornerstone of current malaria treatment. The development of artemisinin resistance in
Plasmodium falciparum
poses a major threat to malaria control and elimination. Recognized first in the Greater Mekong subregion of Southeast Asia nearly 20 years ago, artemisinin resistance has now been documented in Guyana, South America, in Papua New Guinea, and most recently, it has emerged
de novo
in East Africa (Rwanda, Uganda, South Sudan, Tanzania, Ethiopia, Eritrea, and eastern DRC) where it has now become firmly established. Artemisinin resistance is associated with mutations in the propeller region of the
Pf
Kelch gene, which play a causal role, although the parasites’ genetic background also makes an important contribution to the phenotype. Clinically, artemisinin resistance manifests as reduced parasiticidal activity and slower parasite clearance and thus an increased risk of treatment failure following artemisinin-based combination therapy (ACT). This results from the loss of artemisinin activity against the younger circulating ring stage parasites. This loss of activity is likely to diminish the life-saving advantage of artesunate in the treatment of severe falciparum malaria. Gametocytocidal and thus transmission blocking activities are also reduced. At current levels of resistance, artemisinin-resistant parasites still remain susceptible at the trophozoite stage of asexual development, and so, artemisinin still contributes to the therapeutic response. As ACTs are the most widely used antimalarial drugs in the world, it is essential from a malaria control perspective that ACT cure rates remain high. Better methods of identifying uncomplicated hyperparasitemia, the main cause of ACT treatment failure, are required so that longer courses of treatment can be given to these high-risk patients. Reducing the use of artemisinin monotherapies will reduce the continued selection pressure which could lead potentially to higher levels of artemisinin resistance. Triple artemisinin combination therapies should be deployed as soon as possible to protect the ACT partner drugs and thereby delay the emergence of higher levels of resistance. As new affordable antimalarial drugs are still several years away, the control of artemisinin resistance must depend on the better use of available tools.
Combinatorial control of type IVa pili formation by the four polarized regulators MglA, SgmX, FrzS, and SopA
Authors: Oklitschek Michel , Carreira Luís António Menezes , Muratoğlu Memduha , Søgaard-Andersen Lotte , Treuner-Lange Anke
Published: October 2024

Type IVa pili (T4aP) are widespread and enable bacteria to translocate across surfaces. T4aP engage in cycles of extension, surface adhesion, and retraction, thereby pulling cells forward. Accordingly, the number and localization of T4aP are critical to efficient translocation. Here, we address how T4aP formation is regulated in
Myxococcus xanthus
, which translocates with a well-defined leading and lagging cell pole using T4aP at the leading pole. This localization is orchestrated by the small GTPase MglA and its downstream effector SgmX that both localize at the leading pole and recruit the PilB extension ATPase to the T4aP machinery at this pole. Here, we identify the previously uncharacterized protein SopA and show that it interacts directly with SgmX, localizes at the leading pole, stimulates polar localization of PilB, and is important for T4aP formation. We corroborate that MglA also recruits FrzS to the leading pole, and FrzS stimulates SgmX recruitment. In addition, FrzS and SgmX separately recruit SopA. Precise quantification of T4aP-formation and T4aP-dependent motility in various mutants supports a model whereby the main pathway for stimulating T4aP formation is the MglA/SgmX pathway. FrzS stimulates this pathway by recruiting SgmX and SopA. SopA stimulates the MglA/SgmX pathway by stimulating the function of SgmX, likely by promoting the SgmX-dependent recruitment of PilB to the T4aP machinery. The architecture of the MglA/SgmX/FrzS/SopA protein interaction network for orchestrating T4aP formation allows for combinatorial regulation of T4aP levels at the leading cell pole resulting in discrete levels of T4aP-dependent motility.

IMPORTANCE

Type IVa pili (T4aP) are widespread bacterial cell surface structures with important functions in translocation across surfaces, surface adhesion, biofilm formation, and virulence. T4aP-dependent translocation crucially depends on the number of pili. To address how the number of T4aP is regulated, we focused on
M. xanthus
, which assembles T4aP at the leading cell pole and is a model organism for T4aP biology. Our results support a model whereby the four proteins MglA, SgmX, FrzS, and the newly identified SopA protein establish a highly intricate interaction network for orchestrating T4aP formation at the leading cell pole. This network allows for combinatorial regulation of the number of T4aP resulting in discrete levels of T4aP-dependent motility.
Vibrio cholerae
: a fundamental model system for bacterial genetics and pathogenesis research
Authors: van Kessel Julia C. , Camilli Andrew
Published: October 2024

Species of the
Vibrio
genus occupy diverse aquatic environments ranging from brackish water to warm equatorial seas to salty coastal regions. More than 80 species of
Vibrio
have been identified, many of them as pathogens of marine organisms, including fish, shellfish, and corals, causing disease and wreaking havoc on aquacultures and coral reefs. Moreover, many
Vibrio
species associate with and thrive on chitinous organisms abundant in the ocean. Among the many diverse
Vibrio
species, the most well-known and studied is
Vibrio cholerae
, discovered in the 19th century to cause cholera in humans when ingested. The
V. cholerae
field blossomed in the late 20th century, with studies broadly examining
V. cholerae
evolution as a human pathogen, natural competence, biofilm formation, and virulence mechanisms, including toxin biology and virulence gene regulation. This review discusses some of the historic discoveries of
V. cholerae
biology and ecology as one of the fundamental model systems of bacterial genetics and pathogenesis.
Corrinoid salvaging and cobamide remodeling in bacteria and archaea
Authors: Villa Elizabeth A. , Escalante-Semerena Jorge C.
Published: October 2024

Cobamides (Cbas) are cobalt-containing cyclic tetrapyrroles used by cells from all domains of life as co-catalyst of diverse reactions. There are several structural features that distinguish Cbas from one another. The most relevant of those features discussed in this review is the lower ligand, which is the nucleobase of a ribotide located in the lower face of the cyclic tetrapyrrole ring. The above-mentioned ribotide is known as the nucleotide loop, which is attached to the ring by a short linker. In Cbas, the nucleobase of the ribotide can be benzimidazole or derivatives of it, purine or derivatives of it, or phenolic compounds. Given the importance of Cbas in prokaryotic metabolism, it is not surprising that prokaryotes have evolved enzymes that cleave part or the entire nucleotide loop. This function is advantageous when Cbas contain nucleobases that somehow interfere with the function of Cba-dependent enzymes in the organism. After cleavage, Cbas are rebuilt via the nucleotide loop assembly (NLA) pathway, which includes enzymes that activate the nucleobase and the ring intermediate, followed by condensation of activated intermediates and a final dephosphorylation reaction. This exchange of nucleobases is known as Cba remodeling. The NLA pathway is used to salvage Cba precursors from the environment.
Cyclosporine may reduce the risk of symptomatic COVID-19 in patients with systemic lupus erythematosus: a retrospective cohort study
Authors: Li He-Jun , Lin Shu-Huan , Wang Yan-Qing , Chen Ling , Zheng Xiang-Xiong , Wei Li-Xin
Published: October 2024

This study aimed to explore the effect of cyclosporine (CsA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in systemic lupus erythematosus (SLE) patients to provide a valuable reference for clinical treatment strategies in the context of the long-term risk of SARS-CoV-2 infection. SLE patients who visited the Rheumatology Outpatient Department of Fujian Medical University Union Hospital between 1 May and 31 October 2022 were included. Data on SARS-CoV-2 infection in patients between 1 November 2022 and 31 July 2023 were obtained by telephone follow-up. Patients were divided into two groups according to whether CsA was used during the observation period: the glucocorticoid or hydroxychloroquine group and the CsA group. To assess the robustness of the results, Data sets 1 and 2 were established to be analyzed independently. Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for symptomatic coronavirus disease (COVID-19). A total of 184 patients were included, among whom 129 were definite symptomatic COVID-19 patients; 29 were presumptive symptomatic COVID-19 patients; and 4 had signs and symptoms of COVID-19, but tested negative for SARS-CoV-2 in a virological test. According to the multivariable-adjusted models, CsA was associated with lower odds of symptomatic COVID-19 (
P
= 0.042, OR = 0.316, 95% CI: 0.104–0.959 in Data set 1 and
P
= 0.021, OR = 0.257, 95% CI: 0.081–0.812 in Data set 2). CsA is associated with lower odds of contracting symptomatic COVID-19. The use of CsA may be considered an appropriate therapeutic option for disease management in patients with rheumatic diseases who have severe disease activity and persistent SARS-CoV-2 infection.

IMPORTANCE

Our study indicated that cyclosporine may reduce the risk of symptomatic COVID-19 in systemic lupus erythematosus patients in spite of its immunosuppressive effects. This study provides a reference for clinical treatment strategies for AIIRD patients in the context of the long-term risk of SARS-CoV-2 infection.
Cohort profile: an observational population-based cohort study on COVID-19 vaccine effectiveness in the Netherlands – the VAccine Study COVID-19 (VASCO)
Authors: Huiberts Anne J , Hoeve Christina E , Kooijman Marjolein N , de Melker Hester E , Hahné Susan JM , Grobbee Diederick E , van Binnendijk Rob , den Hartog Gerco , van de Wijgert Janneke HHM , van den Hof Susan , Knol Mirjam J
Published: October 2024

Purpose

VAccine Study COVID-19 (VASCO) is a cohort study with a 5-year follow-up that was initiated when COVID-19 vaccination was introduced in the Netherlands. The primary objective is to estimate real-world vaccine effectiveness (VE) of COVID-19 vaccines against SARS-CoV-2 infection in the Netherlands, overall and in four subpopulations defined by age and medical risk.

Participants

The cohort consists of 45 547 community-dwelling participants aged 18–85 years who were included irrespective of their COVID-19 vaccination status or intention to get vaccinated. A medical risk condition is present in 4289 (19.8%) of 21 679 individuals aged 18–59 years, and in 9135 (38.3%) of 23 821 individuals aged 60–85 years. After 1 year of follow-up, 5502 participants had dropped out of the study. At inclusion and several times after inclusion, participants are asked to take a self-collected fingerprick blood sample in which nucleoprotein and spike protein receptor binding domain-specific antibody concentrations are assessed. Participants are also asked to complete monthly digital questionnaires in the first year, and 3 monthly in years 2–5, including questions on sociodemographic factors, health status, COVID-19 vaccination, SARS-CoV-2-related symptoms and testing results, and behavioural responses to COVID-19 measures.

Findings to date

VASCO data have been used to describe VE against SARS-CoV-2 infection of primary vaccination, first and second booster and bivalent boosters, the impact of hybrid immunity on SARS-CoV-2 infection and VE against infectiousness. Furthermore, data were used to describe antibody response following vaccination and breakthrough infections and to investigate the relation between antibody response and reactogenicity.

Future plans

VASCO will be able to contribute to policy decision-making regarding future COVID-19 vaccination. Furthermore, VASCO provides an infrastructure to conduct further studies and to respond to changes in vaccination campaigns and testing policy, and new virus variants.

Trial registration number

NL9279.
Screening, diagnosis, treatment and outcomes of developmental dysplasia of the hip in Brazilian population: a scoping review protocol
Authors: Jaleca Patrícia Eduarda Conrado Martins Ro , Liggio Daniel , Lam Sheila , Arora Sana , Schaeffer Emily , Grangeiro Patricia Moreno
Published: October 2024

Introduction

Developmental dysplasia of the hip (DDH) includes a spectrum of clinical and imaging findings at birth or early infancy. The circumstances in which this condition is detected and managed may be heterogeneous in Brazil owing to its large territory and regional socio-economic differences. Mapping DDH perspectives in a country is fundamental for designing guidelines and strategies for public policy. This scoping review aims to map the available literature related to screening, diagnosis, treatment and outcomes of DDH in the Brazilian population to provide an overview of this condition and to describe regional variations in presentation and management across the country.

Methods and analysis

This study will follow the methods outlined in the Joanna Briggs Institute Reviewers manual for conducting a scoping review. Relevant publications will be first searched in PubMed/MEDLINE, Scientific Electronic Library Online, Web of Science, Scopus, “Biblioteca virtual em saúde” and “Biblioteca Digital Brasileira de Teses e Dissertações” using search terms developed from a brief preliminary search of those databases. There were no language or date range limitations for study inclusion. Databases will be searched from their inception until February 2024. Titles and abstracts will be analysed by two or more independent reviewers to assess them against the inclusion criteria for the review. The search results and study inclusion process will be reported in full in the final version of the scoping review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review (PRISMA-ScR) flowchart. The resulting data will be recorded and organised to present the key information contained in all examined articles.

Ethics and dissemination

This review will include existing available studies and does not require a specific ethical review or approval. The final study will be submitted for presentation at conferences that focus on Brazilian healthcare and publication in peer-reviewed journals. This scoping review protocol was registered in the Open Science Framework. DOI registration (https://doi.org/10.17605/OSF.IO/V3AYH).