bluuebunny/crossref_metadata_2025 huggingface dataset:
Inferring the extinction risk of marine fish to inform global conservation priorities
Authors: Loiseau Nicolas , Mouillot David , Velez Laure , Seguin Raphaël , Casajus Nicolas , Coux Camille , Albouy Camille , Claverie Thomas , Duhamet Agnès , Fleure Valentine , Langlois Juliette , Villéger Sébastien , Mouquet Nicolas
Published: August 2024

While extinction risk categorization is fundamental for building robust conservation planning for marine fishes, empirical data on occurrence and vulnerability to disturbances are still lacking for most marine teleost fish species, preventing the assessment of their International Union for the Conservation of Nature (IUCN) status. In this article, we predicted the IUCN status of marine fishes based on two machine learning algorithms, trained with available species occurrences, biological traits, taxonomy, and human uses. We found that extinction risk for marine fish species is higher than initially estimated by the IUCN, increasing from 2.5% to 12.7%. Species predicted as Threatened were mainly characterized by a small geographic range, a relatively large body size, and a low growth rate. Hotspots of predicted Threatened species peaked mainly in the South China Sea, the Philippine Sea, the Celebes Sea, the west coast Australia and North America. We also explored the consequences of including these predicted species’ IUCN status in the prioritization of marine protected areas through conservation planning. We found a marked increase in prioritization ranks for subpolar and polar regions despite their low species richness. We suggest to integrate multifactorial ensemble learning to assess species extinction risk and offer a more complete view of endangered taxonomic groups to ultimately reach global conservation targets like the extending coverage of protected areas where species are the most vulnerable.
The socioeconomic impacts of Rift Valley fever: A rapid review
Authors: O’Neill Luke , Gubbins Simon , Reynolds Christian , Limon Georgina , Giorgakoudi Kyriaki
Published: August 2024

Rift Valley fever (RVF) is a neglected vector-borne disease which is endemic in many countries across Africa and has seen recent geographical expansions into the Arabian Peninsula. RVF can cause severe infections in both animals and humans. RVF infections in livestock can lead to mass fatalities. In humans, the symptoms are nonspecific and can often lead to misdiagnosis. However, a small proportion progresses to haemorrhagic infection with a significantly higher mortality rate. The culmination of this can cause severe socioeconomic impacts.

This review aims to identify the main socioeconomic impacts caused by RVF outbreaks as well as existing knowledge gaps.

Ninety-three academic and grey papers were selected, covering 19 countries and 10 methodological approaches. A variety of socioeconomic impacts were found across all levels of society: Livestock trade disruptions consequently impacted local food security, local and national economies. Most livestock farmers in endemic countries are subsistence farmers and so rely on their livestock for sustenance and income. RVF outbreaks resulted in a variety of socioeconomic impacts, e.g., the inability to pay for school fees. Main barriers to vaccine uptake in communities were lack of access, funds, interest along with other social aspects. The occupational risks for women (and pregnant women) are largely unknown.

To our knowledge, this is the first review on RVF to highlight the clear knowledge gap surrounding the potential gender differences on risks of RVF exposure, as well as differences on occupational health risk in pastoral communities. Further work is required to fill the gaps identified in this review and inform control policies.
Development of a Core Outcome Measure Instrument; "LeishCOM_LCL”, for Localised Cutaneous Leishmaniasis
Authors: Ranasinghe Shalindra , Senarathne Sujai , Somaratne Vijani , Lacey Charles J. N. , Jayakody Surangi , Wickramasinghe Amila , Kahawita Indira , Goto Hiro , Chatterjee Mitali , Lindoso José A. L. , Parkash Vivak , Chaudhuri Surya J. , Wickremasinghe Renu , Das Nilay K. , Kaye Paul M. , Layton Alison M.
Published: August 2024

Background

Localized cutaneous leishmaniasis (LCL) is a chronic ulcerating disease. A literature review identified inconsistencies in clinical trials. The aims of this study were to reach a consensus on the most important domains to measure when assessing LCL, agree on parameters to measure the domains, and develop a tool representing a Core Outcome Set (COS), for use in clinical assessment of LCL.

Methodology & principal findings

A literature review was conducted to identify any existing COS for LCL embracing agreed Outcome Domains, i.e. what to measure and any Outcome Measurement Instruments (OMIs). As no COS was available, potential outcome domains for assessment of LCL were identified through an international collaborative approach using e-consultations and virtual discussions with expert stakeholders (n = 20) from geographically different LCL endemic countries. Subsequent judgmental validation process included a face-to-face multidisciplinary stakeholders’ meeting adopting the Nominal Group Technique. A final consensual agreement on outcome domains and items required to measure these domains was established. “Clinical Cure” was defined as the ideal overall "General Concept". The five Core Outcome Domains included Signs capturing clinical morphology, diameter, and induration of an index lesion with the aid of a palpability score, Treatment Efficacy assessing percentage change in size of the lesion and re-epithelialization compared to baseline, Treatment Impact which included an investigator and patient visual analogue score, and Clinical Sequelae rating pigment change, atrophic and hypertrophic/keloid scars. It was agreed that two open-ended questions should be included to capture some aspects of Health-Related Quality of Life as a means of capturing a patient-focused approach.

Conclusion

LeishCOM_LCL was generated to reflect a COS for LCL. This captured demographic details, agreed outcome domains and measures to assess these domains. Validation of LeishCOM_LCL will be reported in a separate paper. Development of a Patient Reported Outcome Measure will be considered in the future.
PathEX: Make good choice for whole slide image extraction
Authors: Yang Xinda , Zhang Ranze , Yang Yuan , Zhang Yu , Chen Kai
Published: August 2024

Background

The tile-based approach has been widely used for slide-level predictions in whole slide image (WSI) analysis. However, the irregular shapes and variable dimensions of tumor regions pose challenges for the process. To address this issue, we proposed PathEX, a framework that integrates intersection over tile (IoT) and background over tile (BoT) algorithms to extract tile images around boundaries of annotated regions while excluding the blank tile images within these regions.

Methods

We developed PathEX, which incorporated IoT and BoT into tile extraction, for training a classification model in CAM (239 WSIs) and PAIP (40 WSIs) datasets. By adjusting the IoT and BoT parameters, we generated eight training sets and corresponding models for each dataset. The performance of PathEX was assessed on the testing set comprising 13,076 tile images from 48 WSIs of CAM dataset and 6,391 tile images from 10 WSIs of PAIP dataset.

Results

PathEX could extract tile images around boundaries of annotated region differently by adjusting the IoT parameter, while exclusion of blank tile images within annotated regions achieved by setting the BoT parameter. As adjusting IoT from 0.1 to 1.0, and 1—BoT from 0.0 to 0.5, we got 8 train sets. Experimentation revealed that set C demonstrates potential as the most optimal candidate. Nevertheless, a combination of IoT values ranging from 0.2 to 0.5 and 1-BoT values ranging from 0.2 to 0.5 also yielded favorable outcomes.

Conclusions

In this study, we proposed PathEX, a framework that integrates IoT and BoT algorithms for tile image extraction at the boundaries of annotated regions while excluding blank tiles within these regions. Researchers can conveniently set the thresholds for IoT and BoT to facilitate tile image extraction in their own studies. The insights gained from this research provide valuable guidance for tile image extraction in digital pathology applications.
A conserved C-terminal domain of TamB interacts with multiple BamA POTRA domains in Borreliella burgdorferi
Authors: Hall Kari T. , Kenedy Melisha R. , Johnson David K. , Hefty P. Scott , Akins Darrin R.
Published: August 2024

Lyme disease is the leading tick-borne infection in the United States, caused by the pathogenic spirochete Borreliella burgdorferi, formerly known as Borrelia burgdorferi. Diderms, or bacteria with dual-membrane ultrastructure, such as B. burgdorferi, have multiple methods of transporting and integrating outer membrane proteins (OMPs). Most integral OMPs are transported through the β-barrel assembly machine (BAM) complex. This complex consists of the channel-forming OMP BamA and accessory lipoproteins that interact with the five periplasmic, polypeptide transport-associated (POTRA) domains of BamA. Another system, the translocation and assembly module (TAM) system, has also been implicated in OMP assembly and export. The TAM system consists of two proteins, the BamA paralog TamA which has three POTRA domains and the inner membrane protein TamB. TamB is characterized by a C-terminal DUF490 domain that interacts with the POTRA domains of TamA. Interestingly, while TamB is found in almost all diderms, including B. burgdorferi, TamA is found almost exclusively in Proteobacteria. This strongly suggests a TamA-independent role of TamB in most diderms. We previously demonstrated that BamA interacts with TamB in B. burgdorferi and hypothesized that this is facilitated by the BamA POTRA domains interacting with the TamB DUF490 domain. In this study, we utilized protein-protein co-purification assays to empirically demonstrate that the B. burgdorferi TamB DUF490 domain interacts with BamA POTRA2 and POTRA3. We also observed that the DUF490 domain of TamB interacts with the accessory lipoprotein BamB. To examine if the BamA-TamB interaction is more ubiquitous among diderms, we examined BamA-TamB interactions in Salmonella enterica serovar Typhimurium (St). Interestingly, even though St encodes a TamA protein that interacts with TamB, we observed that the TamB DUF490 of St interacts with BamA in this organism. Our combined findings strongly suggest that the TamB-BamA interaction occurs independent of the TamA component of the TAM protein export system.
A new extraction method of underglaze brown decorative pattern based on the coupling of single scale gamma correction and gray sharpening
Authors: Fang Tao , Qin Dashu , Zhang Rumeng , Jiang Yu , Rui Xue
Published: August 2024

In order to solve the problem of image quality and morphological characteristics of primary underglaze brown decorative pattern extraction, this paper proposes a method of primary underglaze brown decorative pattern extraction based on the coupling of single scale gamma correction and gray sharpening. The single-scale gamma correction is combined with the gray sharpening method. The single-scale gamma correction improves the contrast and brightness of the image by nonlinear transformation, but may lead to the loss of image detail. Gray sharpening can enhance the high frequency component and improve the clarity of the image, but it will introduce noise. Combining these two technologies can compensate for their shortcomings. The experimental results show that this method can improve the efficiency of last element underglaze brown decorative pattern extraction by enhancing the image retention detail and reducing the influence of noise. The experimental results showed that F1Score, Miou(%), Recall, Precision and Accuracy(%) were 0.92745, 0.82253, 0.97942, 0.92458 and 0.92745, respectively.
Unveiling the anti-obesity potential of Kemuning (Murraya paniculata): A network pharmacology approach
Authors: Fatriani Rizka , Pratiwi Firda Agustin Kartika , Annisa Annisa , Septaningsih Dewi Anggraini , Aziz Sandra Arifin , Miladiyah Isnatin , Kusumastuti Siska Andrina , Nasution Mochammad Arfin Fardiansyah , Ramadhan Donny , Kusuma Wisnu Ananta
Published: August 2024

Obesity has become a global issue that affects the emergence of various chronic diseases such as diabetes mellitus, dysplasia, heart disorders, and cancer. In this study, an integration method was developed between the metabolite profile of the active compound of Murraya paniculata and the exploration of the targeting mechanism of adipose tissue using network pharmacology, molecular docking, molecular dynamics simulation, and in vitro tests. Network pharmacology results obtained with the skyline query technique using a block-nested loop (BNL) showed that histone acetyltransferase p300 (EP300), peroxisome proliferator-activated receptor gamma (PPARG), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) are potential targets for treating obesity. Enrichment analysis of these three proteins revealed their association with obesity, thermogenesis, energy metabolism, adipocytokines, fat cell differentiation, and glucose homeostasis. Metabolite profiling of M. paniculata leaves revealed sixteen active compounds, ten of which were selected for molecular docking based on drug-likeness and ADME results. Molecular docking results between PPARG and EP300 with the ten active compounds showed a binding affinity value of ≤ -5.0 kcal/mol in all dockings, indicating strong binding. The stability of the protein-ligand complex resulting from docking was examined using molecular dynamics simulations, and we observed the best average root mean square deviation (RMSD) of 0.99 Å for PPARG with trans-3-indoleacrylic acid, which was lower than with the native ligand BRL (2.02 Å). Furthermore, the RMSD was 2.70 Å for EP300 and the native ligand 99E, and the lowest RMSD with the ligand (1R,9S)-5-[(E)-2-(4-Chlorophenyl)vinyl]-11-(5-pyrimidinylcarbonyl)-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-dien-6-one was 3.33 Å. The in vitro tests to validate the potential of M. paniculata in treating obesity showed that there was a significant decrease in PPARG and EP300 gene expressions in 3T3-L1 mature adipocytes treated with M. paniculata ethanolic extract starting at concentrations 62.5 μg/ml and 15.625 μg/ml, respectively. These results indicate that M. paniculata can potentially treat obesity by disrupting adipocyte maturation and influencing intracellular lipid metabolism.
An adjuvant formulation containing Toll-like Receptor 7 agonist stimulates protection against morbidity and mortality due to Anaplasma marginale in a highly endemic region of west Africa
Authors: Futse James E. , Zumor-Baligi Songliedong , Ashiagbor Charles N. K. , Noh Susan M. , Fox Christopher B. , Palmer Guy H.
Published: August 2024

Efficient cattle production and provision of animal-sourced foods in much of Africa is constrained by vector-borne bacterial and protozoal diseases. Effective vaccines are not currently available for most of these infections resulting in a continuous disease burden that limits genetic improvement. We tested whether stimulation of innate immunity using the Toll-like Receptor (TLR) 7 agonist imiquimod, formulated with saponin and water-in-oil emulsion, would protect against morbidity and mortality due to Anaplasma marginale, a tick-borne pathogen of cattle highly endemic in west Africa. In Trial 1, haplotype matched Friesian x Sanga (F1) A. marginale negative calves were allocated to either the experimental group (n = 10) and injected with the synthetic TLR 7 agonist/saponin formulation or to an untreated control group (n = 10). TLR7 agonist/saponin injected calves responded with significantly elevated rectal temperature, enlarged regional lymph nodes, and elevated levels of IL-6 post-injection as compared to control group calves. All calves were then allowed to graze in pasture for natural exposure to tick transmission. All calves in both groups acquired A. marginale, consistent with the high transmission rate in the endemic region. The need for antibiotic treatment, using pre-existing criteria, was significantly lower in the experimental group (odds ratio for not requiring treatment was 9.3, p = 0.03) as compared to the control group. Despite treatment, 6/10 calves in the control group died, reflecting treatment failures that are typical of anaplasmosis in the acute phase, while mortality in the experimental group was 1/10 (odds ratio for survival was 13.5, p = 0.03). The trial was then repeated using 45 Friesian x Sanga calves per group. In Trial 2, the odds ratios for preventing the need for treatment and for mortality in the TLR7 agonist/saponin experimental group versus the control group were 5.6 (p = 0.0002) and 7.0 (p = 0.004), respectively, reproducing the findings of the initial trial. Together these findings demonstrate that innate immune stimulation using a TLR7 agonist formulated with saponin and water-in-oil emulsion provides significant protection against disease caused by tick borne A. marginale in highly susceptible cross-bred cattle, critically important for their potential to increase productivity for smallholder farmers in Africa.
Status of trace metals and arsenic in sediments and catfish muscles (Clarias gariepinus) from the Eastern Tanzanian basin
Authors: Mayila Edward , Mzula Alexanda , Rumisha Cyrus , Leermakers Martine , Huyghe Filip , Kochzius Marc
Published: August 2024

Trace metals and metalloids are groups of chemical elements that naturally occur in low concentrations and cycle in the environment driven by natural processes and human activities. They have a persistent and bio-accumulative tendency in the environment, and certain trace metals and metalloids have become a public health concern. This study assesses the concentration of eleven trace metals and a metalloid in sediments and catfish muscle from five study sites in the Eastern Tanzanian River basin. Forty catfish tissues and fifteen sediment samples were collected and analyzed using ICP-MS. Concentrations of As, Cd, Co, Pb, and Zn did not exceed the United States Environmental Protection Agency (USEPA) guideline for pollution of sediments, while Al Cr, Al, Mn, and V with values ranging from (118.54 to 70154.55) indicating moderately polluted. The stations Java-Sadaani and Matandu showed the highest Cr, Ni, and Cu concentrations, but the potential ecological risk index (RI) was low (RI < 95). In the catfish muscle tissue, the levels of Cd, Pb, Cu, and Zn did not surpass the EU and FAO/WHO limits and results ranged from 2.22 to 35.22mg/kg. Low levels of accumulation of Cd, Pb, and As were found in this study compared to catfish muscles from other studies, whereas the concentrations of other trace metals and metalloids analyzed had comparable results. Biota/sediment accumulation factors (BSAF) were all < 1. The weekly metal intake (MWI) results ranged from 6.89E-04 to 2.43E+01 μg/know-1week-1, indicating a low risk as the value did not exceed the FAO/WHO established Permissible Tolerable Weekly Intake (PTWI). The non-carcinogenic health risk result THQ was 4.43E-02 and the carcinogenic health risks result HI was 4.42E-05 which indicated tolerable levels of risks as both the values of the Target Hazard Quotient (THQ) and the Hazard Index (HI) was < 1, and the carcinogenic target risk (TR) is < 0.0001. The highest TR values were observed for Cr and Ni. We recommend a continued monitoring of the changes in trace metal levels in the environment and biota together with continuous public health education on the dangers of high levels of trace metals.
Can green credit policies improve the digital transformation of heavily polluting enterprises: A quasi-natural experiment based on difference-in-differences
Authors: Zhou Xuan , Yuan Dejia , Geng Zhengwei
Published: August 2024

The digital transformation of the manufacturing industry is closely linked to green credit policies, which jointly promote the development of the manufacturing industry towards a more environmentally friendly, efficient and sustainable development. Based on the research sample of China’s manufacturing A-share listed companies from 2008 to 2022, this paper uses the difference-in- differences (DID) method to analyze the impact of green credit policies on the digital transformation of heavily polluting enterprises. The results show that green credit policies significantly inhibit the digital transformation of heavily polluting enterprises. In terms of the adjustment mechanism, the R&D investment of enterprises and the financial background of senior executives have weakened the inhibitory effect of green credit policies on the digital transformation of heavily polluting enterprises. When the R&D investment is low, the inhibitory effect of the policy is more significant, but with the increase of R&D investment, the inhibitory effect of the policy gradually weakens, indicating that there is a substitution relationship between the two. Enterprises with senior financial expertise have a deeper understanding of financial feasibility and benefit analysis, and are more receptive to the high-risk investment of digital transformation, while their financial network resources can help broaden financing channels, reduce financing constraints, and further reduce the financial difficulty of digital transformation. In addition, the green credit policy has a stronger inhibitory effect on the digital transformation of non-state-owned enterprises and enterprises that do not hold bank shares. The conclusions of this paper are expected to provide some policy implications for the subsequent green credit policies in promoting the digital transformation of the manufacturing industry.
Analysis of coupled coordination and spatial interaction effects between digital and tourism economy in the Yangtze River Delta region
Authors: Yang Zeyun , Sang Senyao , Zhu Yaru
Published: August 2024

The coupled and coordinated development of the digital economy and tourism economy has become an inevitable choice for achieving high-quality development in both sectors. This paper proposes a conceptual index system using entropy weight method and coupling coordination degree model for analysis of the coupling coordination relationship between digital economy and tourism economy. After that, the paper introduces the Moran’s Index to examines the spatial heterogeneous effects of coupling coordination degree. This framework is applied to 41 cities in the Yangtze River Delta region during 2011–2021. The results show that the temporal changes of the coupling coordination relationship between digital economy and tourism economy in 41 cities are quite satisfactory, while the regional differences are large. Furthermore, the coupling degree between digital economy and tourism economy shows the strong spatial agglomeration effect, and the spatial proximity of regions with similar integration indicates that the "Matthew Effect" gradually highlights the clustering of high and low levels. Based on the results of analysis, this paper finally puts forward several policy recommendations to provide a referential path for the integration of digital economy and tourism.
Structural and compositional differences in gallery and spiny forests of Southern Madagascar: Implications for conservation of lemur and tree species
Authors: Mondragón-Botero Ariadna , Riera Bernard , Rasamimanana Hantanirina , Razafindrakoto Suzy , Warme Eric , Powers Jennifer S.
Published: August 2024

Madagascar’s unique dry forests, particularly gallery and spiny forests, face severe threats and are significantly understudied, leaving only a fraction of the original extent intact. Thus, there is a critical need for characterizing, conserving, and restoring this diverse forest ecosystem. Conducting extensive floristic surveys and environmental analyses, we investigated structural and compositional differences between the gallery and spiny forests, as well as within distinct gallery forest sites in Berenty Reserve in the south of the island. We also evaluated differences in habitat quality between the spiny and gallery forests for three species of diurnal lemurs in the reserve, and analyzed the current population trend of the tamarind trees, a species of ecological and cultural importance in Madagascar. Our findings revealed that the spiny and gallery forests differed in composition and structure, confirming the unique ecological characteristics of gallery forests and the underexplored richness of spiny forests. Spiny forests exhibited higher species richness despite a comparatively lower sampling effort, emphasizing the need for focused conservation efforts in these overlooked ecosystems. Tamarind populations, vital for lemur nutrition, showed signs of inadequate regeneration suggesting a recruitment bottleneck, possibly due to factors like a lowering water table, brown lemur foraging habits, or shifts in environmental conditions. Urgent interventions, including enrichment plantations, were recommended to ensure the survival of this keystone species. Contrasting botanical and lemur-centric perspectives revealed that while spiny and gallery forests differed botanically, they offered comparable habitat quality for ring-tailed and sifaka lemurs. However, brown lemurs exhibit a preference for the gallery forest, highlighting the intricate relationship between plant composition and lemur habitat choices. Our study underscores the urgency of expanding our knowledge of Madagascar´s dry forests, and Berenty Reserve, as one of the few remaining protected areas with gallery and spiny forests, serves as a reference for future research in Madagascar’s understudied ecosystems.
Registered report protocol for an e: Health motor skills and physical activity intervention in early childhood education centers- e: Motor skills At Playtime (MAP)
Authors: Palmer Kara K. , Wang Lu
Published: August 2024

Background

Children have alarmingly low levels of competency in fundamental motor skills (FMS) and high levels of physical inactivity. e:health interventions, interventions delivered electronically, are useful tools for intervention in the home through parents, but less is known about the effects of these interventions in early childhood education centers or settings. Therefore, we created the Motor skills At Playtime (MAP) e:health intervention (e:MAP) to be delivered in an early childhood education setting. The goals of this pilot study on e:MAP are to (1) determine the intervention effects on children’s FMS and physical activity and (2) explore the teachers’ perceptions and ability to facilitate e:MAP.

Methods

This pilot study uses a pretest/posttest randomized cluster control design. We will recruit at least 64 children (3.5–5 years of age) enrolled in a single early childhood education center. Children will be randomly assigned at the level of the classroom to an e:MAP group (n~30) or a control group (n~30). Children in classrooms assigned to e:MAP will complete an 8-week intervention. We will collect measures of child FMS and physical activity, and teacher’s perceptions of the program before (pretest) and after the intervention (posttest). FMS measures include process (Test of Gross Motor Development-3rd Edition) and product-oriented scores. Physical activity will be assessed using a 7-day accelerometer wear protocol. Teachers’ perceptions will be assessed through a brief survey. Lastly, we will collect data on teachers’ ability to facilitate e:MAP through a daily survey.

Potential significance

This study will yield novel insights into the effectiveness and feasibility of a health intervention in an early childhood education setting. Results from this work will expand our knowledge of how to harness e:health modalities, which have the potential to significantly expand the distribution and scalability of FMS interventions.
Picroside II suppresses chondrocyte pyroptosis through MAPK/NF-κB/NLRP3 signaling pathway alleviates osteoarthritis
Authors: Wang Fanchen , Xiao Jiacong , Li Miao , He Qi , Wang Xintian , Pan Zhaofeng , Li Shaocong , Wang Haibin , Zhou Chi
Published: August 2024

Background

Picroside II (P-II) is the main bioactive constituent of Picrorhiza Kurroa, a traditional Chinese herb of interest for its proven anti-inflammatory properties. Its beneficial effects have been noted across several physiological systems, including the nervous, circulatory, and digestive, capable of treating a wide range of diseases. Nevertheless, the potential of Picroside II to treat osteoarthritis (OA) and the mechanisms behind its efficacy remain largely unexplored.

Aim

This study aims to evaluate the efficacy of Picroside II in the treatment of osteoarthritis and its potential molecular mechanisms.

Methods

In vitro, we induced cellular inflammation in chondrocytes with lipopolysaccharide (LPS) and subsequently treated with Picroside II to assess protective effect on chondrocyte. We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of Picroside II on cell viability and select the optimal Picroside II concentration for subsequent experiments. We explored the effect of Picroside II on chondrocyte pyroptosis and its underlying molecular mechanisms by qRT-PCR, Western blot (WB) and immunofluorescence. In vivo, we established the destabilization of the medial meniscus surgery to create an OA mouse model. The therapeutic effects of Picroside II were then assessed through Micro-CT scanning, Hematoxylin-eosin (H&E) staining, Safranin O-Fast Green (S&F) staining, immunohistochemistry and immunofluorescence.

Results

In in vitro studies, toluidine blue and CCK-8 results showed that a certain concentration of Picroside II had a restorative effect on the viability of chondrocytes inhibited by LPS. Picroside II notably suppressed the expression levels of caspase-1, IL-18, and IL-1β, which consequently led to the reduction of pyroptosis. Moreover, Picroside II was shown to decrease NLRP3 inflammasome activation, via the MAPK/NF-κB signaling pathway. In vivo studies have shown that Picroside II can effectively reduce subchondral bone destruction and osteophyte formation in the knee joint of mice after DMM surgery.

Conclusions

Our research suggests that Picroside II can inhibit chondrocyte pyroptosis and ameliorate osteoarthritis progression by modulating the MAPK/NF-κB signaling pathway.
Investigation of breast cancer molecular subtype in a multi-ethnic population using MRI
Authors: Ab Mumin Nazimah , Ramli Hamid Marlina Tanty , Wong Jeannie Hsiu Ding , Chiew Seow-Fan , Rahmat Kartini , Ng Kwan Hoong
Published: August 2024

Objectives

Accurate subtyping of breast cancer is crucial for its diagnosis, management, and prognostication. This study aimed to determine the association of magnetic resonance imaging (MRI) breast features with the molecular subtype and aggressiveness of breast cancer in a multi-ethnic population.

Methods

Treatment-naive patients with invasive breast carcinoma were included in this retrospective study. Breast MRI features were recorded based on the American College of Radiology-Breast Imaging Reporting and Data System (ACR-BIRADS) criteria, with tumour size, and apparent diffusion coefficient value (ADC). The statistical association was tested with Pearson Chi-Square Test of Independence for categorical data or the Kruskal-Wallis/ Mann Whitney U test for numerical data between the MRI features and molecular subtype, receptor status, tumour grade, lymphovascular infiltration (LVI) and axillary lymph node (ALN). Multinomial logistic regression was used to test the predictive likelihood of the significant features. The breast cancer subtypes were determined via immunohistochemistry (IHC) and dual-color dual-hapten in-situ hybridization (D-DISH). The expression statuses of ER, PR, and HER-2, LVI, and ALN were obtained from the histopathology report. The ER / PR / HER-2 was evaluated according to the American Society of Clinical Oncology / College of American Pathologists.

Results

The study included 194 patients; 41.8% (n = 81) Chinese, 40.7% (n = 79) Malay, and 17.5% (n = 34) Indian, involving 71.6%(n = 139) luminal-like, 12.9%(n = 25) HER-2 enriched, and 15.5%(n = 30) Triple-negative breast cancer (TNBC). TNBC was associated with rim enhancement (p = 0.002) and peritumoral oedema (p = 0.004). HER-2 enriched tumour was associated with larger tumour size (p = 0.041). Luminal-like cancer was associated with irregular shape (p = 0.005) with circumscribed margin (p = 0.003). Other associations were ER-negative tumour with circumscribed margin (p = 0.002) and PR-negative with round shape (p = 0.001). Tumour sizes were larger in ER-negative (p = 0.044) and PR-negative (p = 0.022). Rim enhancement was significantly associated with higher grade (p = 0.001), and moderate peritumoral oedema with positive axillary lymph node (p = 0.002).

Conclusion

Certain MRI features can be applied to differentiate breast cancer molecular subtypes, receptor status and aggressiveness, even in a multi-ethnic population.
The clinical significance of inflammatory biomarkers, IL6 cytokine, and systemic immune inflammatory index in rabbit model of acute and chronic Methicillin-resistant Staphylococcus epidermidis-induced osteomyelitis
Authors: Ancuța Diana-Larisa , Lovati Arianna Barbara , Coman Cristin
Published: August 2024

Infections are a major complication of open fractures and fracture fixation. In this study, an innovative bioactive medical device was used to experimentally treat MRSE-induced osteomyelitis in rabbit tibia. This paper investigates the clinical significance of inflammatory biomarkers (NLR, PLR, MLR and PMR), SII and IL-6 and assesses their role in the development of osteomyelitis. The main objective is to identify the utility of hematological reports derived from neutrophils, leukocytes, monocytes and platelets in the evolution of implant-related osteomyelitis and the estimation of treatment efficiency. In particular, this study compares the response of these inflammatory markers to different treatments in the presence or absence of bioactive materials and/or topical antibiotics over time. The analysis of the threads showed that NLR, PLR and SII had high values in the acute phase of the disease, so that after chronicization, they decrease. The animals treated with vancomycin nano-functionalized peptide-enriched silk fibroin-coated implants showed lower levels of inflammatory biomarkers compared to the other groups (empty implants and peptide-enriched silk fibroin-coated implants). NLR, PLR and SII, complemented by IL-6 can be used as fairly accurate biomarkers for the diagnosis of osteomyelitis.
Correlations between Achilles tendon moment arm and plantarflexor muscle architecture variables
Authors: Faux-Dugan Logan , Piazza Stephen J.
Published: August 2024

The production of triceps surae plantarflexion moment is complex in that the Achilles tendon moment arm affects the Achilles tendon force by determining the muscle length change and shortening velocity during ankle rotation. In addition, there is evidence for associations between the sizes of muscles and their moment arm at the joints they span. These relationships between muscle architecture and tendon moment arm ultimately affect the muscle’s force generating capacity and are thus important for understanding the roles played by muscles in producing locomotion. The purpose of this study was to investigate in vivo the relationship between architecture of two plantarflexors and the Achilles tendon moment arm in a healthy adult population. Ultrasound-based measurements were made of the architecture (fascicle length, muscle volume, physiological cross-sectional area, and anatomical cross-sectional area) of the lateral and medial gastrocnemius and the Achilles tendon moment arm was assessed using a technique that combined ultrasound imaging and motion analysis. Positive correlations were observed between the length (r = 0.499, p = 0.049) and size variables (muscle volume r = 0.621, p = 0.010; ACSA r = 0.536, p = 0.032) of the lateral gastrocnemius and the Achilles tendon moment arm, but correlations were only observed for size variables (muscle volume r = 0.638, p = 0.008; PCSA r = 0.525, p = 0.037; ACSA r = 0.544, p = 0.029), and not the length, of the medial gastrocnemius. These findings suggest lateral gastrocnemius adapts to moment arms to maintain force production throughout the range of motion across individuals, while the medial gastrocnemius does not and is thus better suited for static force generation.
Mechanical and thermal thresholds before and after application of a conditioning stimulus in healthy Göttingen Minipigs
Authors: Petrucci Mariafrancesca , Spadavecchia Claudia , Rieben Robert , Casoni Daniela
Published: August 2024

Minipigs are widely used in biomedical research for translational studies. However, information about pain elicited by experimental procedures is lacking. Non-invasive methods as quantitative sensory testing and conditioned pain modulation are particularly attractive. Our overarching aim was to explore and refine these methods for assessing post-operative pain in minipigs after myocardial infarction. As first step, we aimed at defining mechanical and thermal thresholds in healthy adults Göttingen Minipigs, evaluating their reliability, and testing their modifications after the application of a conditioning stimulus. Thresholds were assessed at different body sites before and after a painful conditioning stimulus (CS) (cuffed tourniquet) and sham CS (uncuffed tourniquet) in eleven animals. Thresholds’ reliability was assessed using interclass correlation coefficient (ICC). The effect of the CS was assessed calculating absolute change, percentage change of the thresholds and standard error of measurement. Baseline mechanical thresholds (Newton) were: left hindlimb 81 [73; 81]; left forearm 81 [72.1; 81]; right forearm 81 [76; 81]; left chest 80.5 [68; 81]; right chest 81 [76.5; 81]; left neck 81 [70.3; 81]; right neck 74.8 [62.3; 80.5]. Reliability of mechanical thresholds was good at right chest (ICC = 0.835) and moderate at left chest (ICC = 0.591), left hindlimb (ICC = 0.606) and left neck (ICC = 0.518). Thermal thresholds showed poor reliability in all the tested sites. A modulatory effect was present at right chest, but it was seen when both a painful CS and a sham CS was applied. Minipigs tendentially showed a pro-nociceptive profile (i.e. conditioning pain facilitation). The measured thresholds are a reference for future trials in this species. Mechanical thresholds showed to be more reliable and, therefore, more useful, than thermal ones. The pain facilitation might be explained by the phenomenon of stress induced hyperalgesia, but this finding needs to be further investigated with a stricter paradigm.
Virtual reconstruction of stone tool refittings by using 3D modelling and the Blender Engine: The application of the “ReViBE” protocol to the archaeological record
Authors: Sánchez-Martínez Javier , Calmet Katia , Martínez Moreno Jorge , Gilabert Xavier Roda
Published: August 2024

Visual representation of material culture plays a crucial role in prehistoric archaeology, from academic research to public outreach and communication. Scientific illustration is a valuable tool for visualising lithic artefacts and refittings, where technical attributes must be drawn to enhance our understanding of their significance. However, the representation of lithic refittings, which involve dynamic and sequential transformations of a volume, requires an alternative approach to traditional two-dimensional models such as photography or illustration. Advances in imaging technologies have improved our ability to capture and communicate the multifaceted nature of archaeological artefacts. In this context, we present the ReViBE protocol (Refitting Visualisation using Blender Engine), which integrates photogrammetry, 3D modelling and the animation software Blender© for the virtual representation of lithic refittings. This protocol allows the sequential study of core reduction phases and their associated flakes, as well as other aspects related to knapping decision making (core rotations, surface modifications, and direction and position of impact points). Thus, this method allows the visualisation of techno-cognitive aspects involved in core reduction through a step-by-step animation process. In addition, the 3D models and virtual reconstructions generated by ReViBE can be accessed through open repositories, in line with the principles of open science and FAIR (Findable, Accessible, Interoperable, and Reusable) data. This accessibility ensures that data on lithic technology and human behaviour are widely available, promoting transparency and knowledge sharing, and enabling remote lithic analysis. This in turn breaks down geographical barriers and encourages scientific collaboration.
Functional morphology of antennae and sensilla of the fungivore beetle, Triplax ainonia Lewis (Coleoptera: Erotylidae)
Authors: Hou Xiao-Long , Huang Shi-Hui , Hong Ben , Yang Mao-Fa , Luo Chang-Qing
Published: August 2024

The antennal sensilla play an important role in many behavioral activities of insects. The fungivorous beetle Triplax ainonia Lewis (Erotylidae) is an important pest which prefers to feed on Pleurotus mushrooms. In order to clarify the types, number, and distribution of the antennal sensilla of male and female T. ainonia, scanning electron microscopy was used. The results showed that there were five sensillum types on the antennae of adults male and female, including Böhm’s bristles (BB), sensilla chaetica (three subtypes: SC 1, SC 2, and SC 3), sensilla basiconica (three subtypes: SB 1, SB 2, and SB 3), sensilla trichodea (ST), and sensilla styloconica (SS). Among all the sensilla, the number of SB 2 was the most abundant in both sexes. We found that there was no sexually dimorphic in the sensillum types, but there were differences in the number, lengths, and diameters of some sensilla between males and females. Based on the information of the morphology and distribution of the sensilla, the potential functions of the antennal sensilla of T. ainonia adults were discussed. The results of this study provide a basis for further study on the behavioral ecology and electrophysiology of the fungivore beetles of the Erotylidae.
Vancomycin-resistant Staphylococcus aureus (VRSA) can overcome the cost of antibiotic resistance and may threaten vancomycin’s clinical durability
Authors: Blechman Samuel E. , Wright Erik S.
Published: August 2024

Vancomycin has proven remarkably durable to resistance evolution by Staphylococcus aureus despite widespread treatment with vancomycin in the clinic. Only 16 cases of vancomycin-resistant S. aureus (VRSA) have been documented in the United States. It is thought that the failure of VRSA to spread is partly due to the fitness cost imposed by the vanA operon, which is the only known means of high-level resistance. Here, we show that the fitness cost of vanA-mediated resistance can be overcome through laboratory evolution of VRSA in the presence of vancomycin. Adaptation to vancomycin imposed a tradeoff such that fitness in the presence of vancomycin increased, while fitness in its absence decreased in evolved lineages. Comparing the genomes of vancomycin-exposed and vancomycin-unexposed lineages pinpointed the D-alanine:D-alanine ligase gene (ddl) as the target of loss-of-function mutations, which were associated with the observed fitness tradeoff. Vancomycin-exposed lineages exhibited vancomycin dependence and abnormal colony morphology in the absence of drug, which were associated with mutations in ddl. However, further evolution of vancomycin-exposed lineages in the absence of vancomycin enabled some evolved lineages to escape this fitness tradeoff. Many vancomycin-exposed lineages maintained resistance in the absence of vancomycin, unlike their ancestral VRSA strains. These results indicate that VRSA might be able to compensate for the fitness deficit associated with vanA-mediated resistance, which may pose a threat to the prolonged durability of vancomycin in the clinic. Our results also suggest vancomycin treatment should be immediately discontinued in patients after VRSA is identified to mitigate potential adaptations.
Marine sponge microbe provides insights into evolution and virulence of the tubercle bacillus
Authors: Pidot Sacha J. , Klatt Stephan , Ates Louis S. , Frigui Wafa , Sayes Fadel , Majlessi Laleh , Izumi Hiroshi , Monk Ian R. , Porter Jessica L. , Bennett-Wood Vicki , Seemann Torsten , Otter Ashley , Taiaroa George , Cook Gregory M. , West Nicholas , Tobias Nicholas J. , Fuerst John A. , Stutz Michael D. , Pellegrini Marc , McConville Malcolm , Brosch Roland , Stinear Timothy P.
Published: August 2024

Reconstructing the evolutionary origins of Mycobacterium tuberculosis, the causative agent of human tuberculosis, has helped identify bacterial factors that have led to the tubercle bacillus becoming such a formidable human pathogen. Here we report the discovery and detailed characterization of an exceedingly slow growing mycobacterium that is closely related to M. tuberculosis for which we have proposed the species name Mycobacterium spongiae sp. nov., (strain ID: FSD4b-SM). The bacterium was isolated from a marine sponge, taken from the waters of the Great Barrier Reef in Queensland, Australia. Comparative genomics revealed that, after the opportunistic human pathogen Mycobacterium decipiens, M. spongiae is the most closely related species to the M. tuberculosis complex reported to date, with 80% shared average nucleotide identity and extensive conservation of key M. tuberculosis virulence factors, including intact ESX secretion systems and associated effectors. Proteomic and lipidomic analyses showed that these conserved systems are functional in FSD4b-SM, but that it also produces cell wall lipids not previously reported in mycobacteria. We investigated the virulence potential of FSD4b-SM in mice and found that, while the bacteria persist in lungs for 56 days after intranasal infection, no overt pathology was detected. The similarities with M. tuberculosis, together with its lack of virulence, motivated us to investigate the potential of FSD4b-SM as a vaccine strain and as a genetic donor of the ESX-1 genetic locus to improve BCG immunogenicity. However, neither of these approaches resulted in superior protection against M. tuberculosis challenge compared to BCG vaccination alone. The discovery of M. spongiae adds to our understanding of the emergence of the M. tuberculosis complex and it will be another useful resource to refine our understanding of the factors that shaped the evolution and pathogenesis of M. tuberculosis.