bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between oral microbiota and colorectal cancer: A systematic review
Authors: Camañes‐Gonzalvo Sara , Montiel‐Company José María , Lobo‐de‐Mena Miriam , Safont‐Aguilera María José , Fernández‐Diaz Amaya , López‐Roldán Andrés , Paredes‐Gallardo Vanessa , Bellot‐Arcís Carlos
Published: May 2024

This systematic review aims to investigate the microbial basis underlying the association between oral microbiota and colorectal cancer. A comprehensive search was conducted across four databases, encompassing potentially relevant studies published up to April 2024 related to the PECO question: “Is there a differentiation in oral microbial composition between adult patients diagnosed with colorectal cancer compared to healthy patients?”. The Newcastle‐Ottawa Scale was used to evaluate the quality of the studies included. The level of evidence was assessed through the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) tool. Sixteen studies fulfilled the eligibility criteria. Based on low to moderate evidence profile, high levels of certain subspecies within Firmicutes (such as Streptococcus anginosus, Peptostreptococcus stomatis, S. koreensis, and S. gallolyticus), Prevotella intermedia, Fusobacterium nucleatum, and Neisseria oralis were found to be associated with colorectal cancer. Conversely, certain bacteria (e.g., Lachnospiraceae, F. periodonticum, and P. melaninogenica) could exert a symbiotic protective effect against colorectal cancer. Based on existing evidence, it appears that variations in oral microbiota composition exist among individuals with and without colorectal cancer. However, further research is necessary to determine the mechanisms of oral dysbiosis in colorectal carcinogenesis.
Platelet hyperresponsiveness and increased platelet‐neutrophil aggregates in dogs with myxomatous mitral valve disease and pulmonary hypertension
Authors: Duler Laetitia , Visser Lance , Nguyen Nghi , Johnson Lynelle R. , Stern Joshua A. , Li Ronald H. L.
Published: May 2024

Background

Pulmonary hypertension (PH) in dogs with myxomatous mitral valve disease (MMVD) is caused by increased pulmonary venous pressure. Thrombosis, vascular remodeling, and vasoconstriction mediated by platelets could exacerbate PH.

Hypothesis

Dogs with PH will exhibit a hypercoagulable state, characterized by increased platelet activation, platelet‐leukocyte, and platelet‐neutrophil aggregate formation.

Animals

Eleven dogs (≥3.5 kg) diagnosed with MMVD and PH and 10 dogs with MMVD lacking PH.

Methods

Prospective cohort ex vivo study. All dogs underwent echocardiographic examination, CBC, 3‐view thoracic radiographs, and heartworm antigen testing. Severity of PH and MMVD were assessed by echocardiography. Viscoelastic monitoring of coagulation was assessed using thromboelastography (TEG). Platelet activation and platelet‐leukocyte/platelet‐neutrophil interactions were assessed using flow cytometry. Plasma serotonin concentrations were measured by ELISA.

Results

Unstimulated platelets from dogs with MMVD and PH expressed more surface P‐selectin than MMVD controls (P = .03). Platelets from dogs with MMVD and PH had persistent activation in response to agonists. The number of platelet‐leukocyte aggregates was higher in dogs with MMVD and PH compared with MMVD controls (P = .01). Ex vivo stimulation of whole blood resulted in higher numbers of platelet‐neutrophil aggregates in dogs with MMVD and PH (P = .01). Assessment of hypercoagulability based on TEG or plasma serotonin concentrations did not differ between groups.

Conclusion and Clinical Importance

Platelet hyperresponsiveness and increased platelet‐neutrophil interaction occur in dogs with MMVD and PH, suggesting that platelets play a role of in the pathogenesis of PH. Clinical benefits of antiplatelet drugs in dogs with MMVD and PH require further investigation.
Transient vegetation dynamics in a tropical coastal wetland: Sea‐level rise, glycophyte retreat, and incipient loss in plant diversity
Authors: Ross Michael S. , Stoffella Susana L. , Ruiz Pablo L. , Subedi Suresh C. , Meeder John F. , Sah Jay P. , Vidales Rosario , Minchin Peter R. , Scinto Leonard J. , Zhang Keqi
Published: May 2024

Aim and Questions

Sea‐level rise has been responsible for extensive vegetation changes in coastal areas worldwide. The intent of our study was to analyze vegetation dynamics of a South Florida coastal watershed within an explicit spatiotemporal framework that might aid in projecting the landscape's future response to restoration efforts. We also asked whether recent transgression by mangroves and other halophytes has resulted in reduced plant diversity at local or subregional scales.

Location

Florida’'s Southeast Saline Everglades, USA.

Methods

We selected 26 locations, representing a transition zone between sawgrass marsh and mangrove swamp, that was last sampled floristically in 1995. Within this transition zone, leading‐ and trailing‐edge subzones were defined based on plant composition in 1995. Fifty‐two site × time combinations were classified and then ordinated to examine vegetation–environment relationships using 2016 environmental data. We calculated alpha‐diversity using Hill numbers or Shannon–Weiner index species equivalents and compared these across the two surveys. We used a multiplicative diversity partition to determine beta‐diversity from landscape‐scale (gamma) diversity in the entire dataset or in each subzone.

Results

Mangrove and mangrove associates became more important in both subzones: through colonization and establishment in the leading edge, and through population growth combined with the decline of freshwater species in the trailing edge. Alpha‐diversity increased significantly in the leading edge and decreased nominally in the trailing edge, while beta‐diversity declined slightly in both subzones as well as across the study area.

Conclusions

Recent halophyte encroachment in the Southeast Saline Everglades continues a trend evident for almost a century. While salinity is an important environmental driver, species’ responses suggest that restoration efforts based on supplementing freshwater delivery will not reverse a trend that depends on multiple interacting factors. Sea‐level‐rise‐driven taxonomic homogenization in coastal wetland communities develops slowly, lagging niche‐based changes in community structure and composition.
Inflammatory bowel disease and allergic diseases: A Mendelian randomization study
Authors: Li Jiawei , Wang Lijun , Ma Yuqi , Liu Yuan
Published: May 2024

Background

Inflammatory bowel disease (IBD) and allergic diseases possess similar genetic backgrounds and pathogenesis. Observational studies have shown a correlation, but the exact direction of cause and effect remains unclear. The aim of this Mendelian randomization (MR) study is to assess bidirectional causality between inflammatory bowel disease and allergic diseases.

Method

We comprehensively analyzed the causal relationship between inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC) and allergic disease (asthma, Hay fever, and eczema) as a whole, allergic conjunctivitis (AC), atopic dermatitis (AD), allergic asthma (AAS), and allergic rhinitis (AR) by performing a bidirectional Mendelian randomization study using summary‐level data from genome‐wide association studies. The analysis results mainly came from the random‐effects model of inverse variance weighted (IVW‐RE). In addition, multivariate Mendelian randomization (MVMR) analysis was conducted to adjust the effect of body mass index (BMI) on the instrumental variables.

Results

The IVW‐RE method revealed that IBD genetically increased the risk of allergic disease as a whole (OR = 1.03, 95% CI = 1.01–1.04, fdr.p = .015), AC (OR = 1.04, 95% CI = 1.01–1.06, fdr.p = .011), and AD (OR = 1.06, 95% CI = 1.02–1.09, fdr.p = .004). Subgroup analysis further confirmed that CD increased the risk of allergic disease as a whole (OR = 1.02, 95% CI = 1.00–1.03, fdr.p = .031), AC (OR = 1.03, 95% CI = 1.01–1.05, fdr.p = .012), AD (OR = 1.06, 95% CI = 1.02–1.09, fdr.p = 2E−05), AAS (OR = 1.05, 95% CI = 1.02–1.08, fdr.p = .002) and AR (OR = 1.03, 95% CI = 1.00–1.07, fdr.p = .025), UC increased the risk of AAS (OR = 1.02, 95% CI = 0.98–1.07, fdr.p = .038). MVMR results showed that after taking BMI as secondary exposure, the causal effects of IBD on AC, IBD on AD, CD on allergic disease as a whole, CD on AC, CD on AD, CD on AAS, and CD on AR were still statistically significant. No significant association was observed in the reverse MR analysis.

Conclusion

This Mendelian randomized study demonstrated that IBD is a risk factor for allergic diseases, which is largely attributed to its subtype CD increasing the risk of AC, AD, ASS, and AR. Further investigations are needed to explore the causal relationship between allergic diseases and IBD.
The extent of multiallelic, co‐editing of LIGULELESS1 in highly polyploid sugarcane tunes leaf inclination angle and enables selection of the ideotype for biomass yield
Authors: Brant Eleanor J. , Eid Ayman , Kannan Baskaran , Baloglu Mehmet Cengiz , Altpeter Fredy
Published: May 2024

Sugarcane (Saccharum spp. hybrid) is a prime feedstock for commercial production of biofuel and table sugar. Optimizing canopy architecture for improved light capture has great potential for elevating biomass yield. LIGULELESS1 (LG1) is involved in leaf ligule and auricle development in grasses. Here, we report CRISPR/Cas9‐mediated co‐mutagenesis of up to 40 copies/alleles of the putative LG1 in highly polyploid sugarcane (2n = 100–120, x = 10–12). Next generation sequencing revealed co‐editing frequencies of 7.4%–100% of the LG1 reads in 16 of the 78 transgenic lines. LG1 mutations resulted in a tuneable leaf angle phenotype that became more upright as co‐editing frequency increased. Three lines with loss of function frequencies of ~12%, ~53% and ~95% of lg1 were selected following a randomized greenhouse trial and grown in replicated, multi‐row field plots. The co‐edited LG1 mutations were stably maintained in vegetative progenies and the extent of co‐editing remained constant in field tested lines L26 and L35. Next generation sequencing confirmed the absence of potential off targets. The leaf inclination angle corresponded to light transmission into the canopy and tiller number. Line L35 displaying loss of function in ~12% of the lg1 NGS reads exhibited an 18% increase in dry biomass yield supported by a 56% decrease in leaf inclination angle, a 31% increase in tiller number, and a 25% increase in internode number. The scalable co‐editing of LG1 in highly polyploid sugarcane allows fine‐tuning of leaf inclination angle, enabling the selection of the ideotype for biomass yield.
BnaC4.BOR2 mediates boron uptake and translocation in Brassica napus under boron deficiency
Authors: Liu Wei , Xu Fangsen , Ye Xiangsheng , Cai Hongmei , Shi Lei , Wang Sheliang
Published: May 2024

Boron (B) is an essential microelement in plant growth and development. However, the molecular mechanisms underlying B uptake and translocation in Brassica napus are poorly understood. Herein, we identified a low‐B (LB)‐inducible gene, namely BnaC4.BOR2, with high transcriptional activity in root tips, stele cells, leaves, and floral organs. The green fluorescence protein labelled BnaC4.BOR2 protein was localised to the plasma membrane to demonstrate the B efflux activity in yeast and Arabidopsis. BnaC4.BOR2 knockout considerably reduced B concentration in the root and xylem sap, and altered B distribution in different organs at low B supply, exacerbating B sensitivity at the vegetative and reproductive stages. Additionally, the grafting experiment showed that BnaC4.BOR2 expression in the roots contributed more to B deficiency adaptability than that in the shoots. The pot experiments with LB‐soil revealed B concentration in leaves and siliques of BnaC4.BOR2 mutants were markedly reduced, showing an obvious B‐deficient phenotype of ‘flowering without seed setting’ and a considerable reduction in seed yield in B‐deficient soil. Altogether, the findings of this study highlight the crucial role of BnaC4.BOR2 in B uptake and translocation during B. napus growth and seed yield under LB conditions.
BnTX1–BnNCED3 interaction contributes to the ABA biosynthesis response in the Brassica napus–Leptosphaeria maculans pathosystem
Authors: Zou Zhongwei , Liu Fei , Huang Shuanglong , Fernando W. G. Dilantha
Published: May 2024

Abscisic acid (ABA) plays multiple and pivotal roles in plant defence against abiotic and biotic stresses. Blackleg, mainly caused by the fungal pathogen Leptosphaeria maculans, is one of the most devastating diseases in canola (Brassica napus) resulting in significant yield loss worldwide. Few studies have investigated the function of ABA biosynthesis genes in response to fungal pathogens. In this study, we identified and characterized BnNCED3 (9‐cis‐epoxycarotenoid dioxygenease) and BnTX1 (trithorax‐like factor) from B. napus. Transgenic B. napus ‘Westar’ plants overexpressing BnNCED3 showed enhanced adult plant resistance to blackleg infection. Chromatin immunoprecipitation‐quantitative PCR demonstrated that BnTX1 bound to the promoter region of the BnNCED3 gene. However, the overexpression of BnTX1 in transgenic plants decreased adult plant resistance to blackleg pathogen infection. The expression analysis confirmed the abundance of BnNCED3 transcripts was higher in BnTX1‐RNAi knockdown plants than in overexpressing plants. Thus, BnTX1 might play a negative role in regulating BnNCED3 gene expression and hence ABA biosynthesis, thereby affecting plant disease resistance. Our study provides a new model demonstrating how increased ABA levels can enhance plant disease resistance, which may lead to the characterization of minor/quantitative genes in the B. napus–L. maculans interaction.
The relationship between workload and exercise‐induced cardiac troponin elevations is influenced by non‐obstructive coronary atherosclerosis
Authors: Bjorkavoll‐Bergseth Magnus , Erevik Christine , Kleiven Øyunn , Wiktorski Tomasz , Auestad Bjørn , Skadberg Øyvind , Aakre Kristin M. , Eijsvogels Thijs M. H. , Ørn Stein
Published: May 2024

The relationship between exercise‐induced troponin elevation and non‐obstructive coronary artery disease (CAD) is unclear. This observational study assessed non‐obstructive CAD's impact on exercise‐induced cardiac Troponin I (cTnI) elevation in middle‐aged recreational athletes. cTnI levels of 40 well‐trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high‐sensitive cTnI assay 24 h before, and at 3 and 24 h following two high‐intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91‐km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non‐obstructive (<50% obstruction) CAD. A total of 15 individuals had non‐obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post‐exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3–112.4) ng/L vs. 11.6 (6.4–22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7–16.3) vs. 5.0 (2.6–8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post‐exercise (Rho = 0.80, p < 0.001 vs. Rho = −0.20, p = 0.33) and 24‐h post‐exercise (Rho = 0.87, p < 0.001 vs. Rho = −0.13, p = 0.55). Exercise‐induced cTnI elevation was strongly correlated with exercise workload in middle‐aged athletes with non‐obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.
Comparative efficacy and safety of the treatment by Omalizumab for chronic idiopathic urticaria in the general population: A systematic review and network meta‐analysis
Authors: Xu Lan , Yu Han , Xu Shengxian , Wang Yingjun , Cao Yi
Published: May 2024

Background

Omalizumab is the only licensed drug that serves as a third‐line treatment for chronic idiopathic urticaria (CIU). The optimum doses of omalizumab remain controversial. Therefore, this study aims to estimate the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.

Materials and methods

Four databases were searched from the database's creation to April 8, 2023. Several keywords such as omalizumab and urticarias were used to retrieve related studies. The meta‐analytical outcomes were analyzed in R 4.2.1 software and Stata 15.1 software. Cochrane risk‐of‐bias tool Ver. 2 was used to evaluate the risk of bias in randomized controlled trials (RCTs).

Results

In total, 2331 patients were included. Five indexes were employed to assess, including weekly Itch Severity Score (ISS7), weekly Hive Severity Score (HSS7), weekly Urticaria Activity Score (UAS7), Dermatology Life Quality Index (DLQI), and adverse events (AE). A 300 mg dose of omalizumab was the optimum dose to treat CIU, followed by the 150 mg dose. Furthermore, 600 mg of omalizumab only showed a significant difference from the placebo in HSS7. No significant statistical difference was observed in AE. Meta‐regression analysis revealed that time, as a covariate, was statistically significant in the comparison of omalizumab 150 mg with placebo.

Conclusion

300 mg of omalizumab was the optimum dosage to treat CIU patients, with a 150 mg dose also exhibiting good efficacy. Further studies are required to explore the efficacy and safety of different doses of omalizumab in the treatment of CIU patients.
Apolipoprotein E2 Expression Alters Endosomal Pathways in a Mouse Model With Increased Brain Exosome Levels During Aging
Authors: Peng Katherine Y. , Liemisa Braison , Pasato Jonathan , D'Acunzo Pasquale , Pawlik Monika , Heguy Adriana , Penikalapati Sai C. , Labuza Amanda , Pidikiti Harshitha , Alldred Melissa J. , Ginsberg Stephen D. , Levy Efrat , Mathews Paul M.
Published: May 2024

The polymorphic APOE gene is the greatest genetic determinant of sporadic Alzheimer's disease risk: the APOE4 allele increases risk, while the APOE2 allele is neuroprotective compared with the risk‐neutral APOE3 allele. The neuronal endosomal system is inherently vulnerable during aging, and APOE4 exacerbates this vulnerability by driving an enlargement of early endosomes and reducing exosome release in the brain of humans and mice. We hypothesized that the protective effects of APOE2 are, in part, mediated through the endosomal pathway. Messenger RNA analyses showed that APOE2 leads to an enrichment of endosomal pathways in the brain when compared with both APOE3 and APOE4. Moreover, we show age‐dependent alterations in the recruitment of key endosomal regulatory proteins to vesicle compartments when comparing APOE2 to APOE3. In contrast to the early endosome enlargement previously shown in Alzheimer's disease and APOE4 models, we detected similar morphology and abundance of early endosomes and retromer‐associated vesicles within cortical neurons of aged APOE2 targeted‐replacement mice compared with APOE3. Additionally, we observed increased brain extracellular levels of endosome‐derived exosomes in APOE2 compared with APOE3 mice during aging, consistent with enhanced endosomal cargo clearance by exosomes to the extracellular space. Our findings thus demonstrate that APOE2 enhances an endosomal clearance pathway, which has been shown to be impaired by APOE4 and which may be protective due to APOE2 expression during brain aging.
Disease severity in subsequent pregnancies with RhD immunization: A nationwide cohort
Authors: Zwiers Carolien , Slootweg Yolentha M. , Koelewijn Joke M. , Ligthart Peter C. , van der Bom Johanna G. , van Kamp Inge L. , Lopriore Enrico , van der Schoot C. Ellen , Oepkes Dick , de Haas Masja
Published: May 2024

Background and Objectives

To evaluate the severity of haemolytic disease of the foetus and newborn (HDFN) in subsequent pregnancies with RhD immunization and to identify predictive factors for severe disease.

Materials and Methods

Nationwide prospective cohort study, including all pregnant women with RhD antibodies. All women with at least two pregnancies with RhD antibodies and RhD‐positive foetuses were selected. The main outcome measure was the severity of HDFN in the first and subsequent pregnancy at risk. A subgroup analysis was performed for the group of women where RhD antibodies developed after giving birth to an RhD‐positive child and thus after receiving anti‐D at least twice (group A) or during the first pregnancy at risk for immunization (group B).

Results

Sixty‐two RhD immunized women with a total of 150 RhD‐positive children were included. The severity of HDFN increased for the whole group significantly in the subsequent pregnancy (p < 0.001), although it remained equal or even decreased in 44% of women. When antibodies were already detected at first trimester screening in the first immunized pregnancy, after giving birth to an RhD‐positive child (group A), severe HDFN in the next pregnancy was uncommon (22%). Especially when no therapy or only non‐intensive phototherapy was indicated during the first immunized pregnancy (6%) or if the antibody‐dependent cell‐mediated cytotoxicity result remained <10%. Contrarily, women with a negative first trimester screening and RhD antibodies detected later during the first pregnancy of an RhD‐positive child (group B), often before they had ever received anti‐D prophylaxis, were most prone for severe disease in a subsequent pregnancy (48%).

Conclusion

RhD‐mediated HDFN in a subsequent pregnancy is generally more severe than in the first pregnancy at risk and can be estimated using moment of antibody detection and severity in the first immunized pregnancy. Women developing antibodies in their first pregnancy of an RhD‐positive child are at highest risk of severe disease in the next pregnancy.
The effect of anatomic location on porcine models of burn injury and wound healing
Authors: Liu Aiping , Cheong J. Z. Alex , Hassan Sameeha , Wielgat Matthew B. , Meudt Jennifer J. , Townsend Elizabeth Catherine , Shanmuganayagam Dhanansayan , Kalan Lindsay R. , Gibson Angela
Published: May 2024

Porcine models are frequently used for burn healing studies; however, factors including anatomic location and lack of standardised wound methods can impact the interpretation of wound data. The objectives of this study are to examine the influence of anatomical locations on the uniformity of burn creation and healing in porcine burn models. To optimise burn parameters on dorsal and ventral surfaces, ex vivo and in situ euthanized animals were first used to examine the location‐dependence of the burn depth and contact time relationship. The location‐dependent healing in vivo was then examined using burn and excisional wounds at dorsal, ventral, caudal and cranial locations. Lactate dehydrogenase (LDH) and H&E were used to assess burn depth and wound re‐epithelialization. We found that burn depth on the ventral skin was significantly deeper than that of the dorsal skin at identical thermal conditions. Compared with burns created ex vivo, burns created in situ immediately post‐mortem were significantly deeper in the ventral location. In live animals, 2 out of 12 burn wounds were fully re‐epithelialized after 14 days in contrast to complete re‐epithelialization of all excisional wounds. Among the burn wounds, those at the cranial‐dorsal site exhibited faster healing than at the caudal‐dorsal site. This study showed that anatomical location is an important consideration for the consistency of burn depth creation and healing. These data support symmetric localization of treatment and control for comparative assessment of burn healing in porcine models to prevent misinterpretation of results and increase the translatability of findings to humans.
Optimizing Coupled Fluid-Structure Simulations for Nuclear-Relevant Geometries
Authors: Vivaldi Daniele , Ricciardi Guillaume
Published: May 2024

The numerical simulation of fluid-structure interactions (FSI) has gained interest to study flow-induced vibrations. Nevertheless, the high computational resources required by such simulations can represent a significant limitation for their application to industrial configurations. Therefore, simplified modeling approaches, when physically applicable, can represent an interesting compromise. This can be the case of slender structures (tubes, rods) often encountered in nuclear power plants. In this paper, an Euler–Bernoulli beam finite element model is implemented inside the computational fluid dynamics (CFD) code code_Saturne. With the goal of finding CFD methods less expensive than large eddy simulations (LES), unsteady Reynolds Navier–Stokes (URANS) and hybrid URANS/LES approaches are considered. The resulting fluid-structure model is able to calculate the vibration response of cantilever beams under a fluid flow, avoiding the necessity of CFD-finite element method (FEM) code coupling. The first part of the paper describes the model and its implementation: it allows to perform 2-way explicit fluid-structure coupling, using the Arbitrary Lagrangian-Eulerian approach to account for the structure deformations. Validation test cases are presented in the second part: first, the model is validated in terms of frequency, added mass, and damping for a cylinder vibrating in static air and water; then, the model is validated toward the vortex-induced resonance and lock-in mechanisms for a cylinder subjected to water cross-flow. The model is then applied to a real experimental configuration of two in-line cylinders in water cross-flow: the calculated vibrations are found to be in good agreement with the experimental measurements.
Continuous wave laser-assisted evaporation of halide perovskite thin films from a single stoichiometric source
Authors: Jasti Naga Prathibha , Tirosh Shay , Halder Ansuman , Teblum Eti , Cahen David
Published: May 2024

We report continuous wave laser-assisted evaporation (CLE), a thin film deposition technique that yields phase-pure and stoichiometric thin films of halide perovskites (HaPs) from stoichiometric HaP targets. We use methylammonium lead bromide (MAPbBr3) to demonstrate the ability to grow with CLE well-oriented and smooth thin films on various substrates. Further, we show the broader applicability of CLE by preparing films of several other 3D HaP compounds, viz., methylammonium lead iodide, formamidinium lead bromide, and a 2D one, butylammonium lead iodide. CLE is a single-source, solvent-free, room-temperature process that needs only roughing pump vacuum; it allows the deposition of hybrid organic-inorganic compound films without needing post-thermal treatment or an additional organic precursor source to yield the intended product. The resulting films are polycrystalline and highly oriented. All these features, and the fact that one stoichiometric source serves as the target, make for an attractive, potentially scalable dry deposition approach.
Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control
Authors: Herrera-Arcos Guillermo , Song Hyungeun , Yeon Seong Ho , Ghenand Omkar , Gutierrez-Arango Samantha , Sinha Sapna , Herr Hugh
Published: May 2024

Closed-loop neuroprostheses show promise in restoring motion in individuals with neurological conditions. However, conventional activation strategies based on functional electrical stimulation (FES) fail to accurately modulate muscle force and exhibit rapid fatigue because of their unphysiological recruitment mechanism. Here, we present a closed-loop control framework that leverages physiological force modulation under functional optogenetic stimulation (FOS) to enable high-fidelity muscle control for extended periods of time (>60 minutes) in vivo. We first uncovered the force modulation characteristic of FOS, showing more physiological recruitment and significantly higher modulation ranges (>320%) compared with FES. Second, we developed a neuromuscular model that accurately describes the highly nonlinear dynamics of optogenetically stimulated muscle. Third, on the basis of the optogenetic model, we demonstrated real-time control of muscle force with improved performance and fatigue resistance compared with FES. This work lays the foundation for fatigue-resistant neuroprostheses and optogenetically controlled biohybrid robots with high-fidelity force modulation.
Masks and respirators for prevention of respiratory infections: a state of the science review
Authors: Greenhalgh Trisha , MacIntyre C. Raina , Baker Michael G. , Bhattacharjee Shovon , Chughtai Abrar A. , Fisman David , Kunasekaran Mohana , Kvalsvig Amanda , Lupton Deborah , Oliver Matt , Tawfiq Essa , Ungrin Mark , Vipond Joe
Published: May 2024

This narrative review and meta-analysis summarizes a broad evidence base on the benefits—and also the practicalities, disbenefits, harms and personal, sociocultural and environmental impacts—of masks and masking. Our synthesis of evidence from over 100 published reviews and selected primary studies, including re-analyzing contested meta-analyses of key clinical trials, produced seven key findings. First, there is strong and consistent evidence for airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory pathogens. Second, masks are, if correctly and consistently worn, effective in reducing transmission of respiratory diseases and show a dose-response effect. Third, respirators are significantly more effective than medical or cloth masks. Fourth, mask mandates are, overall, effective in reducing community transmission of respiratory pathogens. Fifth, masks are important sociocultural symbols; non-adherence to masking is sometimes linked to political and ideological beliefs and to widely circulated mis- or disinformation. Sixth, while there is much evidence that masks are not generally harmful to the general population, masking may be relatively contraindicated in individuals with certain medical conditions, who may require exemption. Furthermore, certain groups (notably D/deaf people) are disadvantaged when others are masked. Finally, there are risks to the environment from single-use masks and respirators. We propose an agenda for future research, including improved characterization of the situations in which masking should be recommended or mandated; attention to comfort and acceptability; generalized and disability-focused communication support in settings where masks are worn; and development and testing of novel materials and designs for improved filtration, breathability, and environmental impact.
Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections
Authors: Barker Hailey , Ferraro Mariola J.
Published: May 2024

The endocannabinoid system (ECS), initially identified for its role in maintaining homeostasis, particularly in regulating brain function, has evolved into a complex orchestrator influencing various physiological processes beyond its original association with the nervous system. Notably, an expanding body of evidence emphasizes the ECS’s crucial involvement in regulating immune responses. While the specific role of the ECS in bacterial infections remains under ongoing investigation, compelling indications suggest its active participation in host-pathogen interactions. Incorporating the ECS into the framework of bacterial pathogen infections introduces a layer of complexity to our understanding of its functions. While some studies propose the potential of cannabinoids to modulate bacterial function and immune responses, the outcomes inherently hinge on the specific infection and cannabinoid under consideration. Moreover, the bidirectional relationship between the ECS and the gut microbiota underscores the intricate interplay among diverse physiological processes. The ECS extends its influence far beyond its initial discovery, emerging as a promising therapeutic target across a spectrum of medical conditions, encompassing bacterial infections, dysbiosis, and sepsis. This review comprehensively explores the complex roles of the ECS in the modulation of bacteria, the host’s response to bacterial infections, and the dynamics of the microbiome. Special emphasis is placed on the roles of cannabinoid receptor types 1 and 2, whose signaling intricately influences immune cell function in microbe-host interactions.
Role of the membrane-associated accessory protein (MAAP) in adeno-associated virus (AAV) infection
Authors: Aksu Kuz Cagla , Ning Kang , Hao Siyuan , Cheng Fang , Qiu Jianming
Published: May 2024

Adeno-associated viruses (AAVs) package a single-stranded (ss) DNA genome of 4.7 kb in their capsid of ~20 nm in diameter. AAV replication requires co-infection of a helper virus, such as adenovirus. During the optimization of recombinant AAV production, a small viral nonstructural protein, membrane-associated accessory protein (MAAP), was identified. However, the function of the MAAP in the context of AAV infection remains unknown. Here, we investigated the expression strategy and function of the MAAP during infection of both AAV2 and AAV5 in human embryonic kidney (HEK)293 cells. We found that AAV2 MAAP2 and AAV5 MAAP5 are expressed from the capsid gene (
cap
)-transcribing mRNA spliced from the donor to the second splice site that encodes VP2 and VP3. Thus, this AAV
cap
gene transcribes a multicistronic mRNA that can be translated to four viral proteins, MAAP, VP2, AAP, and VP3 in order. In AAV2 infection, MAAP2 predominantly localized in the cytoplasm, alongside the capsid, near the nuclear and plasma membranes, but a fraction of MAAP2 exhibited nuclear localization. In AAV5 infection, MAAP5 revealed a distinct pattern, predominantly localizing within the nucleus. In the cells infected with an MAAP knockout mutant of AAV2 or AAV5, both viral DNA replication and virus replication increased, whereas virus egress decreased, and the decrease in virus egress can be restored by providing MAAP
in trans
. In summary, MAAP, a novel AAV nonstructural protein translated from a multicistronic viral
cap
mRNA, not only facilitates cellular egress of AAV but also likely negatively affects viral DNA replication during infection.

IMPORTANCE

Recombinant adeno-associated virus (rAAV) has been used as a gene delivery vector in clinical gene therapy. In current gene therapies employing rAAV, a high dose of the vector is required. Consequently, there is a high demand for efficient and high-purity vector production systems. In this study, we demonstrated that membrane-associated accessory protein (MAAP), a small viral nonstructural protein, is translated from the same viral mRNA transcript encoding VP2 and VP3. In AAV-infected cells, apart from its prevalent expression in the cytoplasm with localization near the plasma and nuclear membranes, the MAAP also exhibits notable localization within the nucleus. During AAV infection, MAAP expression increases the cellular egress of progeny virions and decreases viral DNA replication and progeny virion production. Thus, the choice of MAAP expression has pros and cons during AAV infection, which could provide a guide to rAAV production.
Relationship between nephrotoxicity and area under the concentration–time curve of vancomycin in critically ill patients: a multicenter retrospective study
Authors: Ishigo Tomoyuki , Matsumoto Kazuaki , Yoshida Hiroaki , Tanaka Hiroaki , Ibe Yuta , Fujii Satoshi , Fukudo Masahide , Fujihara Hisato , Yamaguchi Fumihiro , Ebihara Fumiya , Maruyama Takumi , Hamada Yukihiro , Samura Masaru , Nagumoi Fumio , Komatsu Toshiaki , Tomizawa Atsushi , Takuma Akitoshi , Chiba Hiroaki , Nishi Yoshifumi , Enoki Yuki , Taguchi Kazuaki , Suzuki Ayako
Published: May 2024

We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration–time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC
24–48h
at the initial therapeutic drug monitoring (TDM) as follows: <500, 500–600, and ≥600 µg·h/mL. The AUC
24–48h
values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56–78) years; 39% women], the AUC
24–48h
<500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC
24–48h
500–600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC
24–48h
≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC
24–48h
500–600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64–17.63] and the AUC
24–48h
≥600 μg·h/mL (hazard ratio 7.0, 95% CI 2.31–21.18) significantly correlated with a higher incidence of AKI compared with the AUC
24-48h
<500 μg·h/mL. In conclusion, we identified an association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI.

IMPORTANCE

Vancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant
Staphylococcus aureus
. However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration–time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets.
Hydrochemical evolution and source mechanisms governing the unusual lithium and boron enrichment in salt lakes of northern Tibet
Authors: Shi Zhiwei , Tan Hongbing , Xue Fei , Li Yulong , Zhang Xiying , Cong Peixin , Santosh M. , Zhang Yu
Published: May 2024

The large-scale salt lakes widely distributed in the Tibetan Plateau provide unique and potential resources for lithium (Li) and boron (B). The concentration and characteristics of elements in these salt lakes resemble those found in geothermal water in northern Tibet, which highlights both as crucial sources of rare elements. This study presents comprehensive analyses of the hydrochemical composition and isotopes of B, strontium (Sr), hydrogen (H), and oxygen (O) in typical salt lakes, along with samples from surrounding springs and rivers in the Bangong-Nujiang suture zone of northern Tibet. The results reveal an extremely negative and anomalous distribution pattern of B isotopes in Zabuye Salt Lake that is closely associated with geothermal water. The enrichment of these elements in other salt lakes in the region is attributed to concentration of evaporation and sediment adsorption. Given the very high elevation of the recharge for geothermal water, the infiltration of salt lakes obviously cannot feed geothermal springs. On the contrary, we correlate the unusual enrichment of Li and B and other resources in salt lakes to geothermal spring discharge. The ultimate origin of these elements lies in magmatic sources, with later water-rock interaction leading to significant enrichment of incompatible elements such as Li, rubidium (Rb), cesium (Cs), and B in the geothermal system. The geothermal springs directly or indirectly fed the salt lakes, and with further evaporation, they became super-scale brine deposits.
Impact of antitumour necrosis factor therapy on surgery in inflammatory bowel disease: a population-based study
Authors: Hawthorne A Barney , Arms-Williams Bradley , Cannings-John Rebecca , Pollok Richard C G , Berry Alexander , Harborne Philip , Trivedi Anjali
Published: May 2024

Objective

It is unclear whether widespread use of biologics is reducing inflammatory bowel disease (IBD) surgical resection rates. We designed a population-based study evaluating the impact of early antitumour necrosis factor (TNF) on surgical resection rates up to 5 years from diagnosis.

Design

We evaluated all patients with IBD diagnosed in Cardiff, Wales 2005–2016. The primary measure was the impact of early (within 1 year of diagnosis) sustained (at least 3 months) anti-TNF compared with no therapy on surgical resection rates. Baseline factors were used to balance groups by propensity scores, with inverse probability of treatment weighting (IPTW) methodology and removing immortal time bias. Crohn’s disease (CD) and ulcerative colitis (UC) with IBD unclassified (IBD-U) (excluding those with proctitis) were analysed.

Results

1250 patients were studied. For CD, early sustained anti-TNF therapy was associated with a reduced likelihood of resection compared with no treatment (IPTW HR 0.29 (95% CI 0.13 to 0.65), p=0.003). In UC including IBD-U (excluding proctitis), there was an increase in the risk of colectomy for the early sustained anti-TNF group compared with no treatment (IPTW HR 4.6 (95% CI 1.9 to 10), p=0.001).

Conclusions

Early sustained use of anti-TNF therapy is associated with reduced surgical resection rates in CD, but not in UC where there was a paradoxical increased surgery rate. This was because baseline clinical factors were less predictive of colectomy than anti-TNF usage. These data support the use of early introduction of anti-TNF therapy in CD whereas benefit in UC cannot be assessed by this methodology.
Effectiveness of community-based diabetes and hypertension prevention and management programmes in Indonesia and Viet Nam: a quasi-experimental study
Authors: Fritz Manuela , Grimm Michael , My Hanh Hoang Thi , Koot Jaap A R , Nguyen Giang Hoang , Nguyen Thi-Phuong-Lan , Probandari Ari , Widyaningsih Vitri , Lensink Robert
Published: May 2024

Introduction

Non-communicable diseases (NCDs) have surpassed infectious diseases as the leading global cause of death, with the Southeast Asian region experiencing a significant rise in NCD prevalence over the past decades. Despite the escalating burden, screening for NCDs remains at very low levels, resulting in undetected cases, premature mortality and high public healthcare costs. We investigate whether community-based NCD prevention and management programmes are an effective solution.

Methods

In Indonesia, we compare participants in the community-based NCD screening and management programmePos Pembinaan Terpadu-Penyakit Tidak Menularwith matched non-participants with respect to their uptake of screening activities, health-related behaviour and knowledge and metabolic risk factors. We use statistical matching to redress a possible selection bias (n=1669). In Viet Nam, we compare members ofIntergenerational Self-Help Clubs, which were offered similar NCD health services, with members of other community groups, where such services were not offered. We can rely on two waves of data and use a double-difference approach to redress a possible selection bias and to measure the impacts of participation (n=1710). We discuss strengths and weaknesses of the two approaches in Indonesia and Viet Nam.

Results

In Indonesia, participants have significantly higher uptake of screening for hypertension and diabetes (+13% from a control mean of 88% (95% CI 9% to 17%); +93% from a control mean of 48% (95% CI 79% to 108%)). In both countries, participants show a higher knowledge about risk factors, symptoms and complications of NCDs (Indonesia: +0.29 SD (0.13–0.45), Viet Nam: +0.17 SD (0.03–0.30)). Yet, the improved knowledge is only partly reflected in improved health behaviour (Viet Nam: fruit consumption +0.33 SD (0.15–0.51), vegetable consumption +0.27 SD (0.04–0.50)), body mass index (BMI) (Viet Nam: BMI −0.07 SD (−0.13 to −0.00)) or metabolic risk factors (Indonesia: systolic blood pressure: −0.13 SD (−0.26 to −0.00)).

Conclusion

Community-based NCD programmes are well suited to increase screening and to transmit health knowledge. Due to their extensive outreach within the community, they can serve as a valuable complement to the screening services provided at the primary healthcare level. Yet, limited coverage, insufficient resources and a high staff turnover remain a problem.

Trial registration number

NCT05239572.
Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study
Authors: Chen Ge , Qian Zhengmin (Min) , Zhang Junguo , Zhang Shiyu , Zhang Zilong , Vaughn Michael G , Aaron Hannah E , Wang Chuangshi , Lip Gregory YH , Lin Hualiang
Published: May 2024

Objective

To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death.

Design

Prospective cohort study.

Setting

UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years).

Participants

415 737 participants, aged 40-69 years, enrolled in the UK Biobank study.

Main outcome measures

Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage).

Results

Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99).

Conclusions

Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.