Multiple Types Research Articles

Development of a head-weighted injury criterion for evaluation of multiple types of AIS 4+ injuries for vulnerable road users

Vulnerable Road users (VRUs) often suffer multiple fatal head injury types simultaneously in road accidents. In this study, a head-weighted injury criterion (HWIC4) was proposed for assessing the risk of head AIS 4+ injuries considering multiple injury types. Firstly, the kinematic characteristics of VRUs in the 50 in-depth accidents were reconstructed by using multi-body system models, and head injuries were reconstructed using eight head kinematic-based injury criteria and eight brain tissue injury criteria via the THUMS (Ver. 4.0.2) head finite element model. The predictive capability of each injury criterion to predict head AIS 4+ injuries was assessed and four better predictors (HIC15, angular acceleration, coup pressure, and maximum principal strain) were selected. The different head injury types and the weighting parameters for each injury type were taken into account in the development of HWIC4. Finally, the effectiveness and evaluation of HWIC4 for head AIS 4+ injury was validated based on the area under of receiver operating characteristic (AUROC) curve and reconstruction results from 10 additional selected accident cases. The results showed that HWIC4 has a good predictive capability for head AIS 4+ injuries with an AUROC of 0.983, which means that HWIC4 is superior and more reliable than a single head injury criterion. This knowledge further improves the capability of head injury criteria to predict head AIS 4+ injuries.

Single-cell chromatin profiling reveals genetic programs activating proregenerative states in nonmyocyte cells.

Cardiac regeneration requires coordinated participation of multiple cell types whereby their communications result in transient activation of proregenerative cell states. Although the molecular characteristics and lineage origins of these activated cell states and their contribution to cardiac regeneration have been studied, the extracellular signaling and the intrinsic genetic program underlying the activation of the transient functional cell states remain largely unexplored. In this study, we delineated the chromatin landscapes of the noncardiomyocytes (nonCMs) of the regenerating heart at the single-cell level and inferred the cis-regulatory architectures and trans-acting factors that control cell type-specific gene expression programs. Moreover, further motif analysis and cell-specific genetic manipulations suggest that the macrophage-derived inflammatory signal tumor necrosis factor-α, acting via its downstream transcription factor complex activator protein-1, functions cooperatively with discrete transcription regulators to activate respective nonCM cell types critical for cardiac regeneration. Thus, our study defines the regulatory architectures and intercellular communication principles in zebrafish heart regeneration.

Stochastic Optimization Approaches for an Operating Room and Anesthesiologist Scheduling Problem

Improving Operating Room, Surgery, and Anesthesiologist Scheduling Using Stochastic and Robust Optimization Efficient planning and scheduling of operating room (OR) activities is crucial for managing costs and delivering high-quality surgical care. However, this task is extremely complex for several reasons. First, it requires coordinating multiple resources, such as ORs and anesthesiologists. Second, in addition to limited OR capacity and time, there is a significant shortage of anesthesiologists required to perform surgeries. Third, surgery durations are uncertain and difficult to predict. Ignoring such uncertainty may lead to substantial overtime, idling, and surgery delays, among other schedule deficiencies. Thus, hospital managers could benefit greatly from advanced methodologies to improve OR utilization, surgical care, and quality as well as to minimize OR operational costs. In “Stochastic Optimization Approaches for an Operating Room and Anesthesiologist Scheduling Problem,” M. Y. Tsang, K. S. Shehadeh, F. E. Curtis, B.R. Hochman, and T. E. Brentjens propose computationally tractable stochastic programming and distributionally robust optimization methodologies for an integrated allocation, assignment, sequencing, and scheduling problem under uncertainty involving multiple ORs, anesthesiologists, and surgery types. Using real-world surgery data and a case study from a health system in New York, they conduct extensive experiments demonstrating the computational efficiency of the proposed methodologies, allowing for their implementation in practice. Moreover, they show the negative consequences of adopting the existing non-integrated approaches and provide valuable practical insights.

Multi-tissue transcriptome-wide association studies identified 235 genes for intrinsic subtypes of breast cancer.

Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown. We performed two multi-tissue TWAS for each BC intrinsic subtype, including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We used summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and triple-negative BC, generated from 106 278 BC cases and 91 477 controls in the Breast Cancer Association Consortium. Overall, we identified 235 genes in 88 loci that were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased the risk of triple-negative BC. Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation that impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC.

Developing intelligent Earth System Models: An AI framework for replacing sub-modules based on incremental learning and its application

In recent years, developing intelligent Earth System Models (ESMs), which integrate artificial intelligence (AI) models to replace ESMs' sub-modules, has shown promising results in enhancing both the accuracy and efficiency of traditional ESMs. A crucial determinant in this process is the quality of training data, which determines what knowledge AI can learn. Delving into specifics, while training with sub-module simulation data bolsters computational swiftness, it can come at the cost of accuracy. On the other hand, training with finer-resolution data (e.g., high-resolution model simulation and observational data) augments accuracy but introduces challenges when coupling AI into ESMs, such as instability or even crashing, and deteriorating accuracy over time. Notably, sub-module simulation and finer-resolution data can complement each other and provide different knowledge to AI. Therefore, our study proposes a novel AI-RepSub framework for replacing sub-modules, which employs the incremental learning (IL) method to learn from multiple data types and preserve previously acquired knowledge when fitting new data. To verify the AI-RepSub's performance, this study chooses to substitute the convection trigger function (CTF) in the Community Earth System Model (CESM), developing a hybrid CESM with an intelligent CTF module (CESM-iCTF). Our online evaluations indicate that CESM-iCTF outperforms CESM in CTF accuracy, computational efficiency, and North Atlantic Oscillation (NAO) hindcast skill while maintaining stability. To the best of our knowledge, this represents the first exploration into AI sub-modules driven by multi-source data in the field of intelligent ESMs, thereby demonstrating the potential of AI to serve as robust replacements for ESMs' sub-modules.

Kidney double positive T cells have distinct characteristics in normal and diseased kidneys

Multiple types of T cells have been described and assigned pathophysiologic functions in the kidneys. However, the existence and functions of TCR+CD4+CD8+ (double positive; DP) T cells are understudied in normal and diseased murine and human kidneys. We studied kidney DPT cells in mice at baseline and after ischemia reperfusion (IR) and cisplatin injury. Additionally, effects of viral infection and gut microbiota were studied. Human kidneys from patients with renal cell carcinoma were evaluated. Our results demonstrate that DPT cells expressing CD4 and CD8 co-receptors constitute a minor T cell population in mouse kidneys. DPT cells had significant Ki67 and PD1 expression, effector/central memory phenotype, proinflammatory cytokine (IFNγ, TNFα and IL-17) and metabolic marker (GLUT1, HKII, CPT1a and pS6) expression at baseline. IR, cisplatin and viral infection elevated DPT cell proportions, and induced distinct functional and metabolic changes. scRNA-seq analysis showed increased expression of Klf2 and Ccr7 and enrichment of TNFα and oxidative phosphorylation related genes in DPT cells. DPT cells constituted a minor population in both normal and cancer portion of human kidneys. In conclusion, DPT cells constitute a small population of mouse and human kidney T cells with distinct inflammatory and metabolic profile at baseline and following kidney injury.

Conditional knockout of the NSD2 gene in mouse intestinal epithelial cells inhibits colorectal cancer progression.

Nuclear receptor-binding SET domain 2 (NSD2) is a histone methyltransferase, that catalyzes dimethylation of lysine 36 of histone 3 (H3K36me2) and is associated with active transcription of a series of genes. NSD2 is overexpressed in multiple types of solid human tumors and has been proven to be related to unfavorable prognosis in several types of tumors. We established a mouse model in which the NSD2 gene was conditionally knocked out in intestinal epithelial cells. We used azoxymethane and dextran sodium sulfate to chemically induce murine colorectal cancer. The development of colorectal tumors were investigated using post-necropsy quantification, immunohistochemistry, and enzyme-linked immunosorbent assay (ELISA). Compared with wild-type (WT) control mice, NSD2fl/fl -Vil1-Cre mice exhibited significantly decreased tumor numbers, histopathological changes, and cytokine expression in colorectal tumors. Conditional knockout of NSD2 in intestinal epithelial cells significantly inhibits colorectal cancer progression.

Toxocara canis infection in multiple types of animals: ophthalmological and pathological observations.

Human ocular toxocariasis (OT), caused by pet roundworm Toxocara canis (Nematoda Ascaridoidea), is a worldwide ocular parasitic infection that poses a severe threat to eyesight, especially in school-aged children. However, the infection process and pathological mechanism of Toxocara are difficult to study in the human body. This study was designed to explore long-term ocular manifestations in different rodents infected with Toxocara canis, uncovering the specific pathological mechanism and migration pathway of larvae after infection. The three types of experimental animals we selected were C57BL/6 mice, Mongolian gerbils and Brown Norway rats. Mice were randomly divided into five groups and infected orally with 1000, 2000, 4000, 8000 and 10,000 T. canis eggs; gerbils were randomly divided into four groups and infected orally with 1000, 2000, 4000 and 10,000 T. canis eggs; rats were randomly divided into three groups and infected orally with 2000, 6000 and 10,000 T. canis eggs. Their ocular changes were closely observed and recorded for at least 2months. We also enucleated the eyeballs of some animals to perform pathological sectioning and hematoxylin-eosin staining. After 3 dpi (days post-infection), hemorrhagic lesions, mechanical injury of the retina and larval migration could be observed in some infected animals. The ocular infection and mortality rates tended to be stable at 7 dpi. Larval tissue, structure disorder and inflammation could be observed in the pathological sections. In conclusion, the mice infected with 2000T. canis eggs and gerbils infected with 1000, 2000 and 4000T. canis eggs showing obvious ocular lesions and lower mortality rates could provide a basis for long-term observation.

Infection status and Molecular types of Rhinovirus among Cases of Acute Respiratory Tract Infections in Luohe City, Henan Province, from 2017 to 2022

Objective: To understand the infection status and molecular types of rhinovirus (RV) among cases of Acute Respiratory Infections (ARIs) in Luohe City, Henan Province, from 2017 to 2022. Methods: From October 2017 to June 2022, clinical and epidemiological data were collected from 2 270 cases of ARIs at Luohe Central Hospital in Henan Province. Throat swab specimens were obtained from these cases. Real-time quantitative polymerase chain reaction (qPCR) was used to screen for RV-positive specimens. Subsequently, the positive samples were subjected to nested reverse transcription polymerase chain reaction (nested RT-PCR) to amplify the full-length VP1 region. Using the MEGA software, along with 169 RV reference strains recommended by the International Committee on Taxonomy of Viruses, a phylogenetic tree was constructed to determine RV types. Results: Among the 2 270 cases of ARIs, there were 1 283 male cases (56.52%). The median age (Q1, Q3) was 3 (1, 6) years, with the population under 5 years old accounting for 68.59% (1 557/2 270). RV was detected in 137 cases (6.04%), of which 68 cases (49.64%) showed co-detection with other viruses, with the most common being co-detection with enterovirus, accounting for 14.60% (20/137). The RV detection rates in the age groups of 0~4 years, 5~14 years, 15~59 years, and≥60 years were 6.42% (100/1 557), 4.69% (21/448), 3.80% (6/158), and 9.35% (10/107), respectively, with no statistically significant differences (χ2=5.310, P=0.150). The overall detection rates of RV before (2017-2019) and during (2020-2022) the COVID-19 pandemic showed no statistically significant difference (χ2=1.823, P=0.177). A total of 109 VP1 sequences were obtained, including 62 types. Among them, RV-A, RV-B, and RV-C had 42, 3, and 17 types respectively. Conclusion: RV is one of the predominant pathogens in ARIs cases in Luohe City, Henan Province, from 2017 to 2022. Multiple types of RV co-circulate without any apparent dominant type.

Estimating the risk of brain metastasis for patients newly diagnosed with cancer

BackgroundBrain metastases (BM) affect clinical management and prognosis but limited resources exist to estimate BM risk in newly diagnosed cancer patients. Additionally, guidelines for brain MRI screening are limited. We aimed to develop and validate models to predict risk of BM at diagnosis for the most common cancer types that spread to the brain.MethodsBreast cancer, melanoma, kidney cancer, colorectal cancer (CRC), small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC) data were extracted from the National Cancer Database to evaluate for the variables associated with the presence of BM at diagnosis. Multivariable logistic regression (LR) models were developed and performance was evaluated with Area Under the Receiver Operating Characteristic Curve (AUC) and random-split training and testing datasets. Nomograms and a Webtool were created for each cancer type.ResultsWe identify 4,828,305 patients from 2010-2018 (2,095,339 breast cancer, 472,611 melanoma, 407,627 kidney cancer, 627,090 CRC, 164,864 SCLC, and 1,060,774 NSCLC). The proportion of patients with BM at diagnosis is 0.3%, 1.5%, 1.3%, 0.3%, 16.0%, and 10.3% for breast cancer, melanoma, kidney cancer, CRC, SCLC, and NSCLC, respectively. The average AUC over 100 random splitting for the LR models is 0.9534 for breast cancer, 0.9420 for melanoma, 0.8785 for CRC, 0.9054 for kidney cancer, 0.7759 for NSCLC, and 0.6180 for SCLC.ConclusionsWe develop accurate models that predict the BM risk at diagnosis for multiple cancer types. The nomograms and Webtool may aid clinicians in considering brain MRI at the time of initial cancer diagnosis.

Robust fake-post detection against real-coloring adversaries

We design warning mechanisms for detecting fake-post on online social networks using crowd signals without significantly affecting the real-post propagation. Building on a recent algorithm where all users assign a real or fake tag to any post, we now consider that users can exhibit adversarial or non-cooperative behavior while tagging. To analyze this system, we introduce and study the total-current population-dependent branching process with multiple death types. We highlight the limitations of the existing mechanism in handling adversaries and propose improved mechanisms that perform effectively even with limited user-specific parameter knowledge. Our theoretical findings are validated through Monte-Carlo simulations.

On the rocks: Biogeography and floristic identity of rocky ecosystems in eastern South America

AbstractThe geodiversity of rocky ecosystems includes diverse plant communities with specific names, but their continental‐scale floristic identity and the knowledge on the role of macroclimate remain patchy. Here, we assessed the identity of plant communities in eastern Brazil across multiple types of rocky landscapes and evaluated the relative importance of climatic variables in constraining floristic differentiation. We provided lists of diagnostic species and an assessment of the conservation status of the identified floristic groups. We compiled a data set of 151 sites (4498 species) from rocky ecosystems, including campos rupestres, campos de altitude, granitic‐gneiss lowland inselbergs, and limestone outcrops. We used unsupervised clustering analysis followed by ANOSIM to assess floristic groups among sites. We performed a random forest variable selection to test whether the identified floristic groups occupy distinct climatic spaces. Six groups (lithobiomes) segregated floristically according to lithology and climate. Alongside campos de altitude and limestone outcrops, inselbergs were divided according to the biome in which they occur (Atlantic Forest or Caatinga), and campos rupestres were largely segregated according to their lithological matrix (ironstone or quartzitic). Plant communities of Caatinga inselbergs were more similar to limestone outcrops, while Atlantic Forest inselbergs communities resembled campos de altitude. The composition of plant communities on outcrops seems to be largely constrained by lithology, but climatic factors are also meaningful for sites with similar lithology. The current network of protected areas does not cover these unique ecosystems and their floristic heterogeneity, with Caatinga inselbergs and limestone outcrops being the least protected.

General framework for ultrafast nonlinear photonics: unifying single and multi-envelope treatments [Invited

Numerical modeling of ultrashort pulse propagation is important for designing and understanding the underlying dynamical processes in devices that take advantage of highly nonlinear interactions in dispersion-engineered optical waveguides. Once the spectral bandwidth reaches an octave or more, multiple types of nonlinear polarization terms can drive individual optical frequencies. This issue is particularly prominent in χ(2) devices where all harmonics of the input pulse are generated and there can be extensive spectral overlap between them. Single-envelope approaches to pulse propagation have been developed to address these complexities; this has led to a significant mismatch between the strategies used to analyze moderate-bandwidth devices (usually involving multi-envelope models) and those used to analyze octave-spanning devices (usually involving models with one envelope per waveguide mode). Here we unify the different strategies by developing a common framework, applicable to any optical bandwidth, that allows for a side-by-side comparison between single- and multi-envelope models. We include both χ(2) and χ(3) interactions in these models, with emphasis on χ(2) interactions. We show a detailed example based on recent supercontinuum generation experiments in a thin-film LiNbO3 on sapphire quasi-phase-matching waveguide. Our simulations of this device show good agreement between single- and multi-envelope models in terms of the frequency comb properties of the electric field, even for multi-octave-spanning spectra. Building on this finding, we explore how the multi-envelope approach can be used to develop reduced models that help build physical insights about new ultrafast photonics devices enabled by modern dispersion-engineered waveguides, and discuss practical considerations for the choice of such models. More broadly, we give guidelines on the pros and cons of the different modeling strategies in the context of device design, numerical efficiency, and accuracy of the simulations.

Bayesian multi-proxy reconstruction of early Eocene latitudinal temperature gradients

Abstract. Accurately reconstructing large-scale palaeoclimatic patterns from sparse local records is critical for understanding the evolution of Earth's climate. Particular challenges arise from the patchiness, uneven spatial distribution, and disparate nature of palaeoclimatic proxy records. Geochemical data typically provide temperature estimates via transfer functions derived from experiments. Similarly, transfer functions based on the climatic requirements of modern taxa exist for some fossil groups, such as pollen assemblages. In contrast, most ecological and lithological data (e.g. coral reefs and evaporites) only convey information on broad climatic requirements. Historically, most large-scale proxy-based reconstructions have used either geochemical or ecological data, but few studies have combined multiple proxy types into a single quantitative reconstruction. Large spatial gaps in existing proxy records have often been bridged by simple averaging, without taking into account the spatial distribution of samples, leading to biased temperature reconstructions. Here, we present a Bayesian hierarchical model to integrate ecological data with established geochemical proxies into a unified quantitative framework, bridging gaps in the latitudinal coverage of proxy data. We apply this approach to the early Eocene climatic optimum (EECO), the interval with the warmest sustained temperatures of the Cenozoic. Assuming the conservation of thermal tolerances of modern coral reefs and mangrove taxa, we establish broad sea surface temperature ranges for EECO coral reef and mangrove sites. We integrate these temperature estimates with the EECO geochemical shallow marine proxy record to model the latitudinal sea surface temperature gradient and global average temperatures of the EECO. Our results confirm the presence of a flattened latitudinal temperature gradient and unusually high polar temperatures during the EECO, which is supported by high-latitude ecological data. We show that integrating multiple types of proxy data, and adequate prior information, has the potential to enhance quantitative palaeoclimatic reconstructions, improving temperature estimates from datasets with limited spatial sampling.

Preparation and properties of polyvinylidene fluoride dielectric nanocomposites for energy storage applications through synergistic addition of ionic liquid‐modified graphene oxide nanosheets and functionalized barium titanate hybrid fillers

AbstractTo tackle the challenge of filler agglomeration and low interfacial bonding strength during manufacturing filled polymer dielectric nanocomposites containing graphene oxide (GO) nanosheets, the author proposed an interface design strategy based on the synergistic hybridization of ionic liquid (IL) modification and different dimensional fillers. GO nanosheets were functionalized by IL, and then polyvinylidene fluoride (PVDF) dielectric nanocomposites (GO‐g‐IL/PVDF) were prepared and evaluated. Based on this, hydroxylated barium titanate BT‐OH@GO‐g‐IL/PVDF ternary nanocomposites were further prepared. A comprehensive analysis of the morphology, mechanical, thermal, electrical, and dielectric properties of the PVDF dielectric nanocomposites was systematically conducted. The results showed that IL was successfully grafted on GO, benefiting an increase in the filler dispersion and interfacial bonding strength. GO‐g‐IL also promoted β‐crystal formation of PVDF and increment of crystallinity. DSC test further revealed that the inclusion of BT‐OH@GO‐g‐IL as dielectric nanofillers promoted the formation of multiple crystal types in PVDF and accelerated the crystallization process. The incorporation of GO‐g‐IL facilitated the formation of localized conductive networks within the PVDF matrix, leading to enhanced electronic displacement polarization and an improved dielectric constant. The dielectric constants of the GO‐g‐IL/PVDF composites containing 2% and 8% of GO‐g‐IL were measured to be 24.28 and 78.46, which were found to be 2.6 and 8.4 times higher than that of pure PVDF. However, the dielectric loss also increased sharply at high nanofiller loading. The dielectric constant and loss of the BT‐OH@GO‐g‐IL/PVDF nanocomposites were found to be 40.32 and 0.38, with a content of 2% for GO‐g‐IL and 20% for BT‐OH.Highlights A facile interface design strategy based on ionic liquid (IL) integrating GO nanosheets and hydroxylated barium titanate (BT‐OH) to form BT‐OH@GO‐g‐IL compounding nanofiller has been proposed. PVDF dielectric nanocomposites containing BT‐OH@GO‐g‐IL compounding nanofiller were systematically investigated and compared. The effects of interfacial interactions between BT‐OH@GO‐g‐IL and PVDF contribute to the uniform dispersion and comprehensive property improvements of PVDF dielectric nanocomposites. This work provides a novel strategy for the fabrication of PVDF dielectric nanocomposites, inspiring the research and development of PVDF in the energy storage applications areas in the future.

Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells.

RNA plays an indispensable role in mammalian cell functions. Cas13, a class of RNA-guided ribonuclease, is a flexible tool for modifying and regulating coding and non-coding RNAs, with enormous potential for creating new cell functions. However, the lack of control over Cas13 activity has limited its cell engineering capability. Here, we present the CRISTAL (Control of RNA with Inducible SpliT CAs13 Orthologs and Exogenous Ligands) platform. CRISTAL is powered by a collection (10 total) of orthogonal split inducible Cas13 effectors that can be turned ON or OFF via small molecules in multiple cell types, providing precise temporal control. Also, we engineer Cas13 logic circuits that can respond to endogenous signaling and exogenous small molecule inputs. Furthermore, the orthogonality, low leakiness, and high dynamic range of our inducible Cas13d and Cas13b enable the design and construction of a robust incoherent feedforward loop, leading to near-perfect and tunable adaptation response. Finally, using our inducible Cas13 effectors, we achieve simultaneous multiplexed control of multiple genes in vitro and in mice. Together, our CRISTAL design represents a powerful platform for precisely regulating RNA dynamics to advance cell engineering and elucidate RNA biology.

Phenotypic and genomic characteristics of clinical IMP-producing Klebsiella spp. Isolates in China

BackgroundIMP-producing Klebsiella spp. (IMPKsp) strains have spread globally, including in China. Currently, the prevalence and genomic characterization of IMPKsp is largely unknown nationwide. Here we aimed to provide a general overview of the phenotypic and genomic characteristics of IMPKsp strains.Methods61 IMPKsp strains were obtained from 13 provinces in China during 2016-2021. All strains were tested for their susceptibility to antimicrobial agents by the microdilution broth method and sequenced with Illumina next-generation sequencing. We performed conjugation experiments on thirteen representative strains which were also sequenced by Oxford nanopore sequencing technology to characterize blaIMP-encoding plasmids.ResultsWe find that all IMPKsp strains display multidrug-resistant (MDR) phenotypes. All strains belong to 27 different STs. ST307 emerges as a principal IMP-producing sublineage. blaIMP-4 is found to be the major isoform, followed by blaIMP-38. Seven incompatibility types of blaIMP-encoding plasmids are identified, including IncHI5 (32/61, 52.5%), IncN-IncR (10/61, 16.4%), IncFIB(K)-HI1B (7/61, 11.5%), IncN (5/61, 8.2%), IncN-IncFII (2/61, 3.3%), IncFII (1/61, 1.6%) and IncP (1/61, 1.6%). The strains carrying IncHI5 and IncN plasmids belong to diverse ST types, indicating that these two plasmids may play an important role in the transmission of blaIMP genes among Klebsiella spp. strains.ConclusionsOur results highlight that multi-clonal transmission, multiple genetic environments and plasmid types play a major role in the dissemination process of blaIMP genes among Klebsiella spp. IncHI5 type plasmids have the potential to be the main vectors mediating the spread of the blaIMP genes in Klebsiella spp.

Knowledge, awareness and decision making of population visiting north indian institute towards dental implant as a treatment modality: a cross-sectional study.

The knowledge and awareness surrounding dental implants have significantly increased over the years, driven by advancements in technology, improved educational resources, and increased accessibility to dental care. Despite their widespread use, it is essential to assess the level of knowledge and awareness among patients regarding dental implants. The purpose of the present study is to measure the knowledge, awareness and decision making in dental implant therapy in North Indian population. An analytical closed ended questionnaire based study. A cross-sectional well structured questionnaire survey was conducted amongst 300 out patients randomly either by interview or Google form to assess the knowledge and awareness about dental implant as a treatment modality. There were seven questions which were close ended multiple choice type concerning patient knowledge and 10 questions for assessing awareness and decision making towards dental implants. Date was collected and descriptive analysis was done. 43.67 % of population was either well informed or moderately informed about replacement of missing teeth. For replacement of missing tooth, most of them (83 %) had the knowledge of dental implant therapy. Dentist was the main source of information about implants. 90.67 % studied population believed that implants provide better treatment because of increased chewing efficiency of implants as compared to removable partial dentures or fixed partial dentures. 86.67 % patients thought that implantologist is better qualified that general dental surgeon. 94 % patients were keen to know more about implants. There is non-significant difference in knowledge and awareness as well as decision making for males and females (p<0.05). People have partial knowledge about dental implants and there is need of spreading awareness about implant therapy in the region. Dentist plays a crucial role for dissemination of knowledge. Cost is a constraining factor for this implant therapy to be chosen as a treatment modality.

Effects of drought-induced stress on nematode communities in aquatic and terrestrial habitats of the Nebraska Sandhills

IntroductionGlobal change events (e.g., worsening drought) are increasing environmental stress in a variety of terrestrial and aquatic habitats. The degree to which communities in soils and sediments are driven by temporal environmental changes across multiple habitat types from the same region is not clear.MethodsWe used nematodes, a common bioindicator of soil and sediment health, to determine how community diversity and composition are altered by rising alkalinity across lakes, shorelines, and prairies in the western Nebraska Sandhills. We sampled these three habitats from five lake basins spanning an alkalinity gradient (pH 7–11) across three years (2019, 2020, 2021). During our sampling, the Sandhills experienced a range of drought intensities, with 2019 being a wet year, followed by severe drought in 2020, and abnormally dry/moderate drought in 2021. To determine if diversity and composition of nematodes responded to increased alkalinity and drought-induced stress we used different modelling approaches, including Random Forest and pairwise comparisons.Results and discussionOverall, nematode diversity in lakes was most affected by increasing alkalinity over time, whereas in shorelines and prairies diversity was most reliant on bacterial diversity and potential nematode-nematode interactions. In comparison to shorelines and prairies, community composition in lakes was the least variable and consistently driven by pH and lake water levels. In contrast, compositions in the shorelines and prairies were more variable and explained at varying degrees by pH, year, lake basin, and climate-associated variables. In addition, relative abundance and compositional nature of select copious taxa were highly unpredictable, indicating potential instability in these habitats. Future research is necessary to address the ecologic stability of the Sandhills and determine where conservation efforts are most needed.

Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.

Lenvatinib is a multitargeted tyrosine kinase inhibitor capable of promoting apoptosis, suppressing angiogenesis, inhibiting tumor cell proliferation, and modulating the immune response. In multiple cancer types, lenvatinib has presented manageable safety and is currently approved as an effective first-line therapy. However, with the gradual increase in lenvatinib application, the inevitable progression of resistance to lenvatinib is becoming more prevalent. A series of recent researches have reported the mechanisms underlying the development of lenvatinib resistance in tumor therapy, which are related to the regulation of cell death or proliferation, histological transformation, metabolism, transport processes, and epigenetics. In this review, we aim to outline recent discoveries achieved in terms of the mechanisms and potential predictive biomarkers of lenvatinib resistance as well as to summarize untapped approaches available for improving the therapeutic efficacy of lenvatinib in patients with various types of cancers.