bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of AMPK activation in
Echinococcus granulosus
sensu stricto limits the parasite’s glucose metabolism and survival
Authors: Yan Mingzhi , Liu Hui , Su Yansen , Bi Xiaojuan , Yang Ning , Lin Renyong , Lü Guodong
Published: February 2024

Cystic echinococcosis (CE) is a zoonotic parasitic disease caused by larvae of the
Echinococcus granulosus sensu lato
(s.l.) cluster. There is an urgent need to develop new drug targets and drug molecules to treat CE. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a serine/threonine protein kinase consisting of α, β, and γ subunits, plays a key role in the regulation of energy metabolism. However, the role of AMPK in regulating glucose metabolism in
E. granulosus
s.l. and its effects on parasite viability is unknown. In this study, we found that targeted knockdown of EgAMPKα or a small-molecule AMPK inhibitor inhibited the viability of
E. granulosus sensu stricto
(s.s.) and disrupted the ultrastructure. The results of
in vivo
experiments showed that the AMPK inhibitor had a significant therapeutic effect on
E. granulosus
s.s.-infected mice and resulted in the loss of cellular structures of the germinal layer. In addition, the inhibition of the EgAMPK/EgGLUT1 pathway limited glucose uptake and glucose metabolism functions in
E. granulosus
s.s.. Overall, our results suggest that EgAMPK can be a potential drug target for CE and that inhibition of EgAMPK activation is an effective strategy for the treatment of disease.
A direct PCR approach with low-biomass insert opens new horizons for molecular sciences on cryptogam communities
Authors: Jung Patrick , Briegel-Williams Laura , Werner Lina , Jost Emily , Schultz Matthias , Nürnberg Dennis J. , Grube Martin , Lakatos Michael
Published: February 2024

Cyanobacteria, green algae, lichens, and other cryptogams play crucial roles in complex microbial systems such as biological soil crusts of arid biomes or biofilms in caves. Molecular investigations on environmental samples or isolates of these microorganisms are often hampered by their dense aggregation, small size, or metabolism products which complicate DNA extraction and subsequent PCRs. Our work presents various examples of how a direct DNA extraction and PCR method relying on low biomass inserts can overcome these common problems and discusses additional applications of the workflow including adaptations.
Antagonistic activity of
Phaeobacter piscinae
against the emerging fish pathogen
Vibrio crassostreae
in aquaculture feed algae
Authors: Roager Line , Athena-Vasileiadi Despoina , Gram Lone , Sonnenschein Eva C.
Published: February 2024

The globally important production of fish and shellfish in aquaculture is challenged by disease outbreaks caused by pathogens such as
Vibrio crassostreae
. These outbreaks not only lead to substantial economic loss and environmental damage, but treatment with antibiotics can also lead to antibiotic resistance affecting human health. Here, we evaluated the potential of probiotic bacteria, specifically the newly identified strain
Phaeobacter piscinae
S26, to counteract these threats in a sustainable manner. Through a systematic assessment of the antagonistic effect of
P. piscinae
S26 against
V. crassostreae
DMC-1, particularly within the context of algal feed systems, the study demonstrates the effectiveness of
P. piscinae
S26 as probiotic and thereby provides a strategic pathway for addressing disease outbreaks in aquaculture. This finding has the potential of significantly contributing to the long-term stability of the industry, highlighting the potential of probiotics as an efficient and environmentally conscious approach to safeguarding aquaculture productivity against the adverse impact of pathogens.
Klebsiella pneumoniae
K2 capsular polysaccharide degradation by a bacteriophage depolymerase does not require trimer formation
Authors: Ye Ting-Juan , Fung Kit-Man , Lee I-Ming , Ko Tzu-Ping , Lin Chia-Yi , Wong Chia-Ling , Tu I-Fan , Huang Tzu-Yin , Yang Feng-Ling , Chang Yu-Pei , Wang Jin-Town , Lin Tzu-Lung , Huang Kai-Fa , Wu Shih-Hsiung
Published: February 2024

K2-capsular
Klebsiella pneumoniae
is a hypervirulent pathogen that causes fatal infections. Here, we describe a phage tailspike protein, named K2-2, that specifically depolymerizes the K2 capsular polysaccharide (CPS) of
K. pneumoniae
into tetrasaccharide repeating units. Nearly half of the products contained
O
-acetylation, which was thought crucial to the immunogenicity of CPS. The product-bound structures of this trimeric enzyme revealed intersubunit carbohydrate-binding grooves, each accommodating three tetrasaccharide units of K2 CPS. The catalytic residues and the key interactions responsible for K2 CPS recognition were identified and verified by site-directed mutagenesis. Further biophysical and functional characterization, along with the structure of a tetrameric form of K2-2, demonstrated that the formation of intersubunit catalytic center does not require trimerization, which could be nearly completely disrupted by a single-residue mutation in the C-terminal domain. Our findings regarding the assembly and catalysis of K2-2 provide cues for the development of glycoconjugate vaccines against
K. pneumoniae
infection.

IMPORTANCE

Generating fragments of capsular polysaccharides from pathogenic bacteria with crucial antigenic determinants for vaccine development continues to pose challenges. The significance of the C-terminal region of phage tailspike protein (TSP) in relation to its folding and trimer formation remains largely unexplored. The polysaccharide depolymerase described here demonstrates the ability to depolymerize the K2 CPS of
K. pneumoniae
into tetrasaccharide fragments while retaining the vital
O
-acetylation modification crucial for immunogenicity. By carefully characterizing the enzyme, elucidating its three-dimensional structures, conducting site-directed mutagenesis, and assessing the antimicrobial efficacy of the mutant enzymes against K2
K. pneumoniae
, we offer valuable insights into the mechanism by which this enzyme recognizes and depolymerizes the K2 CPS. Our findings, particularly the discovery that trimer formation is not required for depolymerizing activity, challenge the current understanding of trimer-dependent TSP activity and highlight the catalytic mechanism of the TSP with an intersubunit catalytic center.
Herptile gut microbiomes: a natural system to study multi-kingdom interactions between filamentous fungi and bacteria
Authors: Vargas-Gastélum Lluvia , Romer Alexander S. , Ghotbi Marjan , Dallas Jason W. , Alexander N. Reed , Moe Kylie C. , McPhail Kerry L. , Neuhaus George F. , Shadmani Leila , Spatafora Joseph W. , Stajich Jason E. , Tabima Javier F. , Walker Donald M.
Published: February 2024

Reptiles and amphibians (herptiles) are some of the most endangered and threatened species on the planet and numerous conservation strategies are being implemented with the goal of ensuring species recovery. Little is known, however, about the gut microbiome of wild herptiles and how it relates to the health of these populations. Here, we report results from the gut microbiome characterization of both a broad survey of herptiles, and the correlation between the fungus
Basidiobolus
, and the bacterial community supported by a deeper, more intensive sampling of
Plethodon glutinosus
, known as slimy salamanders. We demonstrate that bacterial communities sampled from frogs, lizards, and salamanders are structured by the host taxonomy and that
Basidiobolus
is a common and natural component of these wild gut microbiomes. Intensive sampling of multiple hosts across the ecoregions of Tennessee revealed that geography and host:geography interactions are strong predictors of distinct
Basidiobolus
operational taxonomic units present within a given host. Co-occurrence analyses of
Basidiobolus
and bacterial community diversity support a correlation and interaction between
Basidiobolus
and bacteria, suggesting that
Basidiobolus
may play a role in structuring the bacterial community. We further the hypothesis that this interaction is advanced by unique specialized metabolism originating from horizontal gene transfer from bacteria to
Basidiobolus
and demonstrate that
Basidiobolus
is capable of producing a diversity of specialized metabolites including small cyclic peptides.

IMPORTANCE

This work significantly advances our understanding of biodiversity and microbial interactions in herptile microbiomes, the role that fungi play as a structural and functional members of herptile gut microbiomes, and the chemical functions that structure microbiome phenotypes. We also provide an important observational system of how the gut microbiome represents a unique environment that selects for novel metabolic functions through horizontal gene transfer between fungi and bacteria. Such studies are needed to better understand the complexity of gut microbiomes in nature and will inform conservation strategies for threatened species of herpetofauna.
Impact of semen microbiota on the composition of seminal plasma
Authors: Baud D. , Zuber A. , Peric A. , Pluchino N. , Vulliemoz N. , Stojanov M.
Published: February 2024

Several studies have found associations between specific bacterial genera and semen parameters. Bacteria are known to influence the composition of their niche and, consequently, could affect the composition of the seminal plasma. This study integrated microbiota profiling and metabolomics to explore the influence of seminal bacteria on semen metabolite composition in infertile couples, revealing associations between specific bacterial genera and metabolite profiles. Amino acids and acylcarnitines were the predominant metabolite groups identified in seminal plasma. Different microbiota profiles did not result in globally diverse metabolite compositions in seminal plasma. Nevertheless, levels of specific metabolites increased in the presence of a dysbiotic microbiota. Urocanate was significantly increased in abnormal semen samples (adjusted
P
-value < 0.001) and enriched in samples dominated by
Prevotella
spp. (
P
-value < 0.05), which was previously linked to a negative impact on semen. Therefore, varying microbiota profiles can influence the abundance of certain metabolites
,
potentially having an immunomodulatory effect, as seen with urocanate.

IMPORTANCE

Male infertility is often considered idiopathic since the specific cause of infertility often remains unidentified. Recently, variations in the seminal microbiota composition have been associated with normal and abnormal semen parameters and may, therefore, influence male infertility. Bacteria are known to alter the metabolite composition of their ecological niches, and thus, seminal bacteria might affect the composition of the seminal fluid, crucial in the fertilization process. Our research indicates that distinct seminal microbiota profiles are not associated with widespread changes in the metabolite composition of the seminal fluid. Instead, the presence of particular metabolites with immunomodulatory functions, such as urocanate, could shed light on the interplay between seminal microbiota and variations in semen parameters.
Two cases of linagliptin-associated bullous pemphigoid resulting in sepsis and endocarditis
Authors: Vanner Michael , Tanner Alexander , Chakera Ali
Published: February 2024

We describe two patients, in their 70s, each presenting to the emergency department, with 6-week histories of progressively developing pruritic bullae. Both individuals had multiple comorbidities, including type 2 diabetes—for which they took linagliptin, chronic kidney disease, hypertension and prosthetic heart valves. Owing to systemic illness and endocarditis secondary to superadded bacterial infections, they both required intensive treatment and prolonged hospital admissions.

Despite the beneficial effect of linagliptin on glycaemic control and its reported cardiovascular and renal safety profiles, we add our cases as evidence of the significant risk of developing bullous pemphigoid while taking this medication. Secondary infection of bullous pemphigoid increased the risk of developing endocarditis, particularly among individuals with a medical history of valve replacement surgery. Considering this, we advocate caution when prescribing this medication.
Delayed onset enophthalmos and hypoglobus mimicking silent sinus syndrome following midface trauma
Authors: Babu Jawahar , Ramachandran Vishal , Jayakumar Naveen Kumar
Published: February 2024

Craniomaxillofacial trauma is primarily diagnosed and managed by oral and maxillofacial surgeons. Among the cases encountered, midface fractures involving orbital walls are highly prevalent. In these fractures, involvement of the orbital walls, particularly floor of the orbit, can lead to considerable aesthetic and functional limitations. From a maxillofacial perspective, indications for surgical repair of orbital floor encompass marked decrease in ocular motility, fracture affecting more than 50% of surface area, an increase in orbital volume exceeding 18% and enophthalmos greater than 2 mm. In the absence of these discernible signs, surgical intervention is not generally indicated. However, in this case, an early adolescent with a history of midface trauma and minimal orbital floor fracture 8 months earlier presented with progressively delayed onset enophthalmos and hypoglobus closely resembling features of silent sinus syndrome. The enophthalmos and hypoglobus were corrected by placing custom-made non-resorbable high-density polyethylene implant in the orbital floor. Postoperative follow-up demonstrated aesthetically and functionally satisfactory outcomes.
Coexistence of nephrogenic systemic fibrosis and calciphylaxis in a gadolinium-naïve, chronic haemodialysis patient
Authors: Adam Mariyam Shiruzima , Jmor Shilan , Elsayed Ahmed , Naz Noshaba
Published: February 2024

We present a case of a man in his 40s who was on haemodialysis for over 20 years presenting with rapidly progressive decline in mobility, associated with fixed flexion deformities of joints and peau d’orange appearance of skin together with areas of ulceration that was concerning for calciphylaxis. Skin biopsies were consistent with both nephrogenic systemic fibrosis and calciphylaxis. He has never had exposure to gadolinium-based contrast agent. His treatment included daily dialysis sessions, which were challenging due to vascular access issues and three times weekly sodium thiosulfate. He rapidly declined in hospital and died within 2 weeks of presentation while being treated for a hospital-acquired pneumonia.
Clinicopathological characterisation ofMTAPalterations in gastrointestinal cancers
Authors: Mauri Gianluca , Patelli Giorgio , Roazzi Laura , Valtorta Emanuele , Amatu Alessio , Marrapese Giovanna , Bonazzina Erica , Tosi Federica , Bencardino Katia , Ciarlo Gabriele , Mariella Elisa , Marsoni Silvia , Bardelli Alberto , Bonoldi Emanuela , Sartore-Bianchi Andrea , Siena Salvatore
Published: February 2024

Background

Methylthioadenosine phosphorylase (MTAP) is an essential metabolic enzyme in the purine and methionine salvage pathway. In cancer,MTAPgene copy number loss (MTAPloss) confers a selective dependency on the related protein arginine methyltransferase 5. The impact ofMTAPalterations in gastrointestinal (GI) cancers remains unknown although hypothetically druggable. Here, we aim to investigate the prevalence, clinicopathological features and prognosis ofMTAPloss GI cancers.

Methods

Cases withMTAPalterations were retrieved from The Cancer Genome Atlas (TCGA) and a real-world cohort of GI cancers profiled by next-generation sequencing. IfMTAPalterations other than loss were found, immunohistochemistry was performed. Finally, we set a case–control study to assessMTAPloss prognostic impact.

Results

Findings across the TCGA dataset (N=1363 patients) and our cohort (N=508) were consistent. Gene loss was the most commonMTAPalteration (9.4%), mostly co-occurring withCDKN2A/Bloss (97.7%). Biliopancreatic and gastro-oesophageal cancers had the highest prevalence ofMTAPloss (20.5% and 12.7%, respectively), being mostly microsatellite stable (99.2%). In colorectal cancer,MTAPloss was rare (1.1%), while mostMTAPalterations were mutations (5/7, 71.4%); among the latter, onlyMTAP-CDKN2Btruncation led to protein loss, thus potentially actionable.MTAPloss did not confer worse prognosis.

Conclusions

MTAPalterations are found in 5%–10% of GI cancers, most frequently biliopancreatic and gastro-oesophageal.MTAPloss is the most common alteration, identified almost exclusively in MSS,CDKN2A/Bloss, upper-GI cancers. OtherMTAPalterations were found in colorectal cancer, but unlikely to cause protein loss and drug susceptibility.
Effect of Magnesium Site Doping on Electrochemical Properties of Mg-Mn Composite Materials and Application of Carpet-Like Sheets Composite Formed by Cr Doping in Aqueous Zinc-Ion Batteries
Authors: Li Ling , Zhou Jiyao , Huang Wei , Pei Xinbin , Zheng Yong , Wei Jingjing
Published: February 2024

Manganese based compounds have very stable electrochemical properties, thus they are widely applied in aqueous zinc-ion battery. However, it is easy to dissolve manganese in the process of charge and discharge, which leads to the collapse of the cathode material structure. In this paper, the composite materials of manganese carbonate and magnesium carbonate were synthesized by hydrothermal method, and its properties were optimized by doping modification. According to the electrochemical tests, the electrochemical performance of the material synthesized with 5% Cr doping is relatively stable. Moreover, with the increase of Cr content, the charge transfer impedance of the material can be significantly reduced. In the cyclic tests, after 60 cycles of charge and discharge under different current densities, and another several cycles at the current density of 50 mA g−1, the capacity rises to 212.01 mAh g−1, higher than the first discharge capacity. SEM tests are also conducted to survey the micro-structure of the material, besides the cube unit, there are also carpet-like sheets made of nano-sized joined petal-like unit, which greatly increases the specific surface area of the material. According to the data of EDS and XPS, the fact that that the types and valence states of elements in the composites were consistent with those in manganese carbonate and magnesium carbonate are confirmed. Through the infrared and Raman tests, the functional groups in the synthesized material are proven to correspond to the molecular formula. From the XRD pattern, no obvious impurity peaks can be observed. With all the data obtained from physical characterization, it can be concluded that the material is mainly composed of manganese carbonate and magnesium carbonate.
Effect of High Current Density Pulses on Performance Enhancement of Optoelectronic Devices
Authors: Rahman Md Hafijur , Glavin Nicholas , Haque Aman , Ren Fan , Pearton Stephen J.
Published: February 2024

Thermal annealing is commonly used in fabrication processing and/or performance enhancement of electronic and opto-electronic devices. In this study, we investigate an alternative approach, where high current density pulses are used instead of high temperature. The basic premise is that the electron wind force, resulting from the momentum loss of high-energy electrons at defect sites, is capable of mobilizing internal defects. The proposed technique is demonstrated on commercially available optoelectronic devices with two different initial conditions. The first study involved a thermally degraded edge-emitting laser diode. About 90% of the resulting increase in forward current was mitigated by the proposed annealing technique where very low duty cycle was used to suppress any temperature rise. The second study was more challenging, where a pristine vertical-cavity surface-emitting laser (VCSEL) was subjected to similar processing to see if the technique can enhance performance. Encouragingly, this treatment yielded a notable improvement of over 20% in the forward current. These findings underscore the potential of electropulsing as an efficient in-operando technique for damage recovery and performance enhancement in optoelectronic devices.
A preclinical systematic review and meta-analysis assessing the effect of biological sex in lipopolysaccharide-induced acute lung injury
Authors: Kuhar Eva , Chander Nikesh , Stewart Duncan J. , Jahandideh Forough , Zhang Haibo , Kristof Arnold S. , Bastarache Julie A. , Schmidt Eric P. , Taljaard Monica , Thebaud Bernard , Engelberts Doreen , Fergusson Dean A. , Lalu Manoj M.
Published: February 2024

It is unclear what effect biological sex has on outcomes of acute lung injury (ALI). Clinical studies are confounded by their observational design. We addressed this knowledge gap with a preclinical systematic review of ALI animal studies. We searched MEDLINE and Embase for studies of intratracheal/intranasal/aerosolized lipopolysaccharide administration (the most common ALI model) that reported sex-stratified data. Screening and data extraction were conducted in duplicate. Our primary outcome was histological tissue injury and secondary outcomes included alveolar-capillary barrier alterations and inflammatory markers. We used a random-effects inverse variance meta-analysis, expressing data as standardized mean difference (SMD) with 95% confidence intervals (CIs). Risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool. We identified six studies involving 132 animals across 11 independent experiments. A total of 41 outcomes were extracted, with the direction of effect suggesting greater severity in males than females in 26/41 outcomes (63%). One study reported on lung histology and found that male mice exhibited greater injury than females (SMD: 1.61, 95% CI: 0.53–2.69). Meta-analysis demonstrated significantly elevated albumin levels (SMD: 2.17, 95% CI: 0.63–3.70) and total cell counts (SMD: 0.80, 95% CI: 0.27–1.33) in bronchoalveolar lavage fluid from male mice compared with female mice. Most studies had an “unclear risk of bias.” Our findings suggest sex-related differences in ALI severity. However, these conclusions are drawn from a small number of animals and studies. Further research is required to address the fundamental issue of biological sex differences in LPS-induced ALI.
Persistence of emphysema following cessation of cigarette smoke exposure requires a susceptibility factor
Authors: Negasi Zerihun Hailemariam , Nommi Naomi , Liu Congjian , Tesfaigzi Yohannes
Published: February 2024

Exposure of mice to cigarette smoke (CS) for 22 wk causes emphysema, but whether emphysema persists after an additional period of 6 mo after cessation of CS exposure has not been reported. In addition, the role of preexisting susceptibility in enhancing the persistence of CS-induced emphysema after exposure to CS has stopped has not been shown. The present study shows that a preexisting susceptibility must be present to enhance CS-induced emphysema after cessation of CS exposure.
Study on Acoustic Emission Characteristics and Damage Evolution Law of Shale under Uniaxial Compression
Authors: Wu Wenjie , Chan Chee-Ming , Gu Yilei , Su Xiaopeng
Published: February 2024

Investigating the correlation between acoustic emission (AE) parameters and damage mechanisms in rock mechanics can help understand rock damage evolution under loading and provide a theoretical basis for engineering support and safety detection. Therefore, this paper presents experimental works on the correlation between AE and failure mechanisms of rock mass under uniaxial compression stress, with the aim of capturing the damage evolution leading to a new damage constitutive model. The experimental results indicate that the uniaxial compression process of shale can be divided into four stages according to AE characteristics. AE signals are minimal during the crack compaction and elastic stages. The crack initiation strength σci, which is approximately 55% of the uniaxial compressive strength, is identified when the cumulative AE counts and damage factor begin to increase slowly. When axial stress reaches the damage strength σcd, which is approximately 80% of the uniaxial compressive strength, a significant number of AE signals are generated. AE phenomena can be observed during the unstable crack development and post‐crack stages. Considering the initial damage to the rock, the damage factor D initially decreases and then increases with increasing cumulative ring‐down counts rather than exhibiting a monotonic increase. The damage factor D is proportional to the cumulative AE counts N in the stage before rock failure.
Effect of Natural Pozzolana on Physical and Mechanical Properties of Concrete
Authors: Fode Tsion Amsalu , Jande Yusufu Abeid Chande , Kivevele Thomas
Published: February 2024

Construction industries are rapidly growing, sacking high amounts of concrete which has a highly dense microstructure with excellent mechanical properties, more durable, and highly eco‐friendly materials. Hence, many of the researchers are interested in solving this problem with replacing concrete by natural pozzolana (NP) which is a supplementary cementitious material mostly from volcanic sources having much active silica content that can improve the durability and mechanical properties of concrete. However, it is not well‐known which common optimum replacement range can give the most desirable concrete properties. So, the present study sought to review the effects of replacing NP from volcanic sources on the durability, physical, mechanical, and microstructural properties of concrete, also, to identify the most common dose of a positive effect as a replacement in concrete. The review shows that many of NP used by different literature from different places satisfy ASTM replacement standard in concrete, especially, based on its chemical compositions. Also, the review observed that employing NP in concrete significantly improves concrete workability, lengthens setting time, and reduces bulk density, porosity, water absorption, and chloride ion migration by making denser concrete microstructure. In general, adding 5%–20% of NP in concrete significantly improves compressive strength, split tensile strength, and flexural strength. Specifically, most of the studies found 15% replacement of NP having volcanic sources can give optimum strength. Besides these, most of the studies indicated that the improvement of the strength was more visible at the concrete age of 7–28 days.
A Psychometric Study of the Student Evidence-Based Practice Scale S-EBPQ-Arabic Version for Use among Undergraduate Nursing Students
Authors: Alharbi Basmah F.
Published: February 2024

Background. Previous studies have demonstrated the significance of evidence-based practice in improving patient care and outcomes. Therefore, integrating evidence-based practice into the health professions’ education curriculum has become a pedagogical priority. However, there is a lack of reliable and valid scales to measure students’ evidence-based practice usage, attitudes, knowledge, and skills in Arab countries. Aim. This study aims to examine the adapted Student Evidence-Based Practice Scale Questionnaire (S-EBPQ) validity at logical statistical level and reliability for use among students in Arabic context. Methods. This cross-sectional study included 233 undergraduate nursing students from a university in Saudi Arabia, who were recruited after translating and pilot testing the S-EBPQ. Three distinctive types of validity including conceptual, content, and face validity were assessed to determine the quality of the questionnaire items logically. Exploratory factor analyses were performed to examine the tool’s structural validity. Additionally, internal consistency was assessed to evaluate reliability. Findings. All items were considered relevant to Arab culture, and no changes were made to any items. The content validity indices for all items were above 0.80 as this was considered an acceptable value. The exploratory factor analysis identified the same four factors (practice, attitude, retrieving and reviewing evidence, and sharing and applying evidence-based practice). All KMO values for the individual items ≥0.876 were also well above the acceptable 0.6 limit. The four-factor structure explained a total variance of 64%, with factor load score λ ≥ 0.455. The total and subscale S-EBPQ scores showed evidence of reliability, with Cronbach’s alpha ≥0.8. Conclusions. This study demonstrated the reliability and validity of the Arabic S-EBPQ version. The study has the potential to advance Arab countries’ understanding of evidence-based practice. S-EBPQ is a validated tool that can be used to assess nursing students’ knowledge of EBP practices. Since educators need to continually evaluate instructional and curricular design in order to meet contemporary nursing needs, this scale can enhance the educational process and enhance students’ competencies.
Existence and Uniqueness of Solutions for Fractional-Differential Equation with Boundary Condition Using Nonlinear Multi-Fractional Derivatives
Authors: Promsakon Chanon , Ansari Intesham , Wetsah Mecieu , Kumar Anoop , Karthikeyan Kulandhaivel , Sitthiwirattham Thanin
Published: February 2024

In this article the existence as well as the uniqueness (EU) of the solutions for nonlinear multiorder fractional-differential equations (FDE) with local boundary conditions and fractional derivatives of different orders (Caputo and Riemann–Liouville) are covered. The existence result is derived from Krasnoselskii’s fixed point theorem and its uniqueness is shown using the Banach contraction mapping principle. To illustrate the reliability of the results, two examples are given.
Synthesis and Characterization of Paclitaxel-Loaded Silver Nanoparticles: Evaluation of Cytotoxic Effects and Antimicrobial Activity
Authors: Tunç Tutku , Hepokur Ceylan , Kari̇per Afşin
Published: February 2024

Carrier system therapies based on combining cancer drugs with nanoparticles have been reported to control tumor growth and significantly reduce the side effects of cancer drugs. We thought that paclitaxel-loaded silver nanoparticles (AgNPs-PTX) were the right carrier to target cancer cells. We also carried out antimicrobial activity experiments as systems formed with nanoparticles have been shown to have antimicrobial activity. In our study, we used easy-to-synthesize and low-cost silver nanoparticles (AgNPs) with biocatalytic and photocatalytic advantages as drug carriers. We investigated the antiproliferative activities of silver nanoparticles synthesized by adding paclitaxel on MCF-7 (breast adenocarcinoma cell line), A549 (lung carcinoma cell line), C6 (brain glioma cell line) cells, and healthy WI-38 (fibroblast normal cell line) cell lines and their antimicrobial activities on 10 different microorganisms. The synthesized AgNPs and AgNPs-PTX were characterized by dynamic light scattering (DLS), scanning transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, and X-ray spectroscopy. The nanoparticles were spherical in shape, with AgNPs ranging in size from 2.32 to 5.6 nm and AgNPs-PTXs from 24.36 to 58.77 nm. AgNPs demonstrated well stability of −47.3 mV, and AgNPs-PTX showed good stability of −25.4 mV. The antiproliferative effects of the synthesized nanoparticles were determined by XTT (tetrazolium dye; 2,3-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-tetrazolium-5-carboxanilide), and the proapoptotic effects were determined by annexin V/propidium iodide (PI) staining. The effect of AgNPs-PTX was more effective, and anticancer activity was higher than PTX in all cell lines. When selectivity indices were calculated, AgNPs-PTX was more selective in the A549 cell line (SI value 6.53 μg/mL). AgNPs-PTX was determined to increase apoptosis cells by inducing DNA fragmentation. To determine the antimicrobial activity, the MIC (minimum inhibitory concentration) test was performed using 8 different bacteria and 2 different fungi. Seven of the 10 microorganisms tested exhibited high antimicrobial activity according to the MIC ≤100 μg/mL standard, reaching MIC values below 100 μg/mL and 100 μg/mL for both AgNPs and AgNPs-PTX compared to reference sources. Compared to standard antibiotics, AgNPs-PTX was highly effective against 4 microorganisms.
Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value
Authors: Igder Somayeh , Zamani Mozhdeh , Fakher Shima , Siri Morvarid , Ashktorab Hassan , Azarpira Negar , Mokarram Pooneh
Published: February 2024

Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.
Interferon Gamma Induces Higher Neutrophil Extracellular Traps Leading to Tumor-Killing Activity in Microsatellite Stable Colorectal Cancer
Authors: Teng Hao-Wei , Wang Tean-Ya , Lin Chun-Chi , Tong Zhen-Jie , Cheng Hsiao-Wei , Wang Hsiang-Tsui
Published: February 2024

Many patients with colorectal cancer do not respond to immune checkpoint blockade (ICB) therapy, highlighting the urgent need to understand tumor resistance mechanisms. Recently, the link between the IFNγ signaling pathway integrity and ICB resistance in the colorectal cancer tumor microenvironment has been revealed. The immunosuppressive microenvironment poses a significant challenge to antitumor immunity in colorectal cancer development. Tumor-associated neutrophils found in tumor tissues exhibit an immunosuppressive phenotype and are associated with colorectal cancer patient prognosis. Neutrophil extracellular traps (NET), DNA meshes containing cytotoxic enzymes released into the extracellular space, may be promising therapeutic targets in cancer. This study showed increased NETs in tumor tissues and peripheral neutrophils of high levels of microsatellite instability (MSI-H) patients with colorectal cancer compared with microsatellite stable (MSS) patients with colorectal cancer. IFNγ response genes were enriched in MSI-H patients with colorectal cancer compared with patients with MSS colorectal cancer. Co-culturing neutrophils with MSI-H colorectal cancer cell lines induced more NET formation and higher cellular apoptosis than MSS colorectal cancer cell lines. IFNγ treatment induced more NET formation and apoptosis in MSS colorectal cancer cell lines. Using subcutaneous or orthotopic CT-26 (MSS) tumor-bearing mice models, IFNγ reduced tumor size and enhanced PD-1 antibody-induced tumor-killing activity, accompanied by upregulated NETs and cellular apoptosis. These findings suggest that IFNγ could be a therapeutic strategy for MSS colorectal cancer.
SCUBE3 Exerts a Tumor-Promoting Effect in Tongue Squamous Cell Carcinoma by Promoting CEBPA Binding to the CCL2 Promoter
Authors: Zhu Minhui , Ma Yi , Wang Wei , Li Meng , Chen Shicai , Liu Fei , Shi Xiaoqiong , Bi Hongsen , Zhang Chen , Nie Fangfei , Zheng Hongliang , Zhang Caiyun
Published: February 2024

Tongue squamous cell carcinoma (TSCC) is the main pathologic subtype of oral cancer, and the current therapeutic effect is far from satisfactory. The signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3) has been shown to be a tumor-promoting factor in several malignancies. However, little is known about the role of SCUBE3 in TSCC. In this study, we identified that SCUBE3 was highly expressed in TSCC. Clinically, high expression of SCUBE3 was positively associated with tumor stage and T stage of TSCC. Functionally, SCUBE3 silence remarkably restrained cell proliferation, migration, and invasion, induced apoptosis as well as cell cycle arrest in G2-phase, and weakened the tumorigenicity of TSCC cells in vivo. Mechanistically, SCUBE3 promoted the direct binding of CCAAT enhancer binding protein alpha (CEBPA) to C-C motif chemokine ligand 2 (CCL2) promoter in TSCC cells. Interestingly, CCL2 overexpression partially reversed the inhibitory effect of SCUBE3 deficiency on TSCC cell viability and migration. Moreover, STAT3 signaling contributed to CCL2-mediated phenotypes in TSCC cells.

Implications:

Our data revealed a tumor-promoting role for SCUBE3 in TSCC via the CEBPA/CCL2/STAT3 axis, which provided new insight into novel potential therapeutic target for TSCC.
Chondromyxoid Fibroma of the Clavicle: A Case Report of a Rare Clinical Entity
Authors: Soares Diogo , Bernardes Francisco , Silva Nuno Vieira , Silva Marta Cerqueira , Lopes Daniel
Published: February 2024

Introduction: Chondromyxoid fibroma is a rare benign cartilaginous tumor that accounts for less than 1% of all bone tumors and involves long bones of the lower extremities more frequently. Therefore, the clavicle is a rare location of involvement for this entity. Case Presentation: The authors report a case of a diaphyseal chondromyxoid fibroma of the right clavicle in a 30-year-old male that was submitted to en bloc resection of the lesion and reconstruction with an autologous tricortical graft from the iliac crest. The post-operative period was uneventful, and the patient had regained excellent function of this right shoulder. At 2 years of follow-up, there was no evidence of a recurrence of the disease. Conclusion: Chondromyxoid fibroma of the clavicle should be included in the differential diagnosis of an indolent growing mass in this anatomic location.
Auswirkungen von erhitzten Tabakerzeugnissen, E-Zigaretten und brennenden Zigaretten auf die kleinen Atemwege und die arterielle Steifigkeit
Authors: Goebel Isabel , Mohr Theresa , Axt Paul N. , Watz Henrik , Trinkmann Frederik , Weckmann Markus , Drömann Daniel , Franzen Klaas F.
Published: February 2024

Mit dem Rauchen aufzuhören ist schwierig. Noch schwieriger ist es, ohne Nikotinersatztherapie rauchfrei zu bleiben. In den letzten Jahren wurden verschiedene Alternativprodukte auf den Markt gebracht, darunter auch erhitzte Tabakerzeugnisse (HTP). In dieser Studie haben wir die akuten Auswirkungen des Konsums von IQOSTM und gloTM (2 HTP) auf die Funktion der kleinen Atemwege und die arterielle Steifigkeit in einem Head-to-Head-Design untersucht, im Vergleich mit brennenden Zigaretten, nikotinfreien E-Zigaretten und einer Scheinrauchergruppe. 17 gesunde Gelegenheitsraucher wurden in eine zentrale 5-armige Crossover-Studie eingeschlossen. Die Parameter der Funktion der kleinen Atemwege und der Hämodynamik wurden zu verschiedenen Zeitpunkten vor und nach dem Konsum mit dem Mobil-O-GraphTM (I.E.M., Stolberg, Deutschland) und dem TremoFlo® c-100 (THORASYS Thoracic Medical Systems Inc., Montreal, QC, Kanada) gemessen. Sowohl die Obstruktion der kleinen Atemwege als auch der Widerstand waren nach dem Konsum von Zigaretten und Tabakersatzprodukten signifikant erhöht. Alle nikotinhaltigen Produkte führten zu einem ähnlichen signifikanten Anstieg des Blutdrucks und der arteriellen Steifigkeit. Die hämodynamischen Parameter waren auch nach dem Konsum von nikotinfreien E-Zigaretten erhöht, aber der Anstieg war kürzer und schwächer als bei nikotinhaltigen Produkten. Wir kommen zu dem Schluss, dass HTP akute schädliche Auswirkungen auf die Funktion der kleinen Atemwege haben, die möglicherweise größer sind als die Auswirkungen brennender Zigaretten, obwohl die Gründe dafür noch nicht geklärt sind. Wie andere nikotinhaltige Produkte führen auch HTP zu einer akuten nikotinbedingten Erhöhung der arteriellen Steifigkeit und des kardiovaskulären Stresses, ähnlich wie bei brennenden Zigaretten, was diese Produkte mit einem erhöhten kardiovaskulären Risiko in Verbindung bringt.
Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice
Authors: Tran Minh H. , Liu Catherine Y. , Naeem Muhammad Usman , Parris Colby L. , Wang Lei
Published: February 2024

Introduction Renal function may be compromised following recovery from kidney insults. Renal functional reserve (RFR) is a measure of the difference between the kidney's maximum capacity and its baseline function which helps identify any areas of the kidney with compromised function. Usually, RFR is evaluated using acute volume expansion (AVE), but this is typically done in anesthetized animals, which may not accurately represent the kidney's complete functional capacity. In this study, we have introduced a novel method that enables AVE to be conducted in conscious mice.
Methods We have implemented this innovative approach in two animal models representing either intact or impaired renal function, specifically utilizing a lower nephron hypertensive model. Mice were implanted with radio-transmitters for mean artery blood pressure (MAP) monitoring during the experiment. After recovery, half of the mice were induced hypertension by right kidney nephrectomy combined with the ligation of the upper branch of the left kidney. For the AVE, a volume equivalent to 5% of the mouse's body weight was administered via intravenous (IV) or intraperitoneal (IP) bolus injection. Subsequently, the mice were individually housed in cages covered with plastic wrap. Urine was collected every hour for a total of 3 hours for the measurement of urine and sodium excretion.
Results The MAP for all normotensive mice were consistent throughout the AVE, but it increased 5-16mmHg in the hypertensive mice upon AVE. Remarkably, conscious mice exhibited a significantly stronger response to IV-administered AVE when compared to anesthetized mice. This response was evident in the increase in urinary flow, which was approximately 170% and 145% higher in conscious normotensive and hypertensive mice, respectively, compared to their respective baselines. In contrast, anesthetized normotensive and hypertensive mice showed only around a 130% and 100% increase in urinary flow, respectively. Additionally, upon AVE, conscious normotensive mice excreted approximately 47% more sodium than conscious hypertensive mice. In contrast, anesthetized normotensive mice excreted only about 30% more sodium than their anesthetized hypertensive counterparts.
Conclusion Performing a kidney stress test with a significant solution load in conscious mice seems to be a superior method for evaluating RFR compared to conducting the test under anesthesia. Assessing kidney clearance while the mice are conscious has the potential to enhance the precision of diagnosing and predicting both acute and chronic kidney diseases.
EFFICIENCY OF APPLICATION OF THE COMBINED HEPATOPROTECTOR IN COMPLEX TREATMENT OF CHRONIC PANCREATITIS WITH CONCOMITANT LIVER DAMAGE
Authors: Babinets L. S. , Kovalchuk K. M.
Published: February 2024

SUMMARY. Comorbidity of chronic pancreatitis (CP) and chronic viral hepatitis C (CVHC) is quite common and problematic, even after etiotropic treatment of viral hepatitis C infection.

The aim – to investigate the state of the functional capacity of the pancreas and general clinical and selected biochemical parameters of patients with CP against the background of treated CVHC under the influence of the proposed complex treatment with the additional inclusion of the hepatotrophic drug heparizin (HZ).

Material and Methods. 45 patients with CP comorbid with CVHC were studied. All patients were examined according to generally accepted algorithms and received a generally accepted complex of treatment according to the protocol (GAT) for CP in accordance with the order of the Ministry of Health of Ukraine No. 638 dated 2014 and CVHC – according to the Clinical Guideline of the Ministry of Health of Ukraine, based on evidence "Viral Hepatitis C" dated 2020. All outpatient patients with a comorbid course of CP and CVHC were divided into 2 groups to study the effectiveness of the proposed correction programs: 1 group (20 patients) received a generally accepted complex of treatment according to the protocol (GAT) for three months, Group 2 (GAT+HZ) – 25 patients with CP and CVHC) – received GAT with the additional inclusion of the hepatotrophic agent Heparizin PLC, 1 capsule 3 times a day after meals for 3 months.

Results. A more significant level of effectiveness of the treatment complex with the additional inclusion of the hepatotrophic drug heparizin was established in relation to this protocol treatment for the restoration of the functional and structural state of the pancreas according to the studied parameters: the content of fecal α-elastase increased by 54.4 % vs. 39.9 %, respectively, and glucose content decreased – by 15.6 % vs. 10.0 %, the co-program score decreased – by 40.2 % vs. 25.1 %, the US score of the software structure decreased – by 74.4 % vs. 33.6 % (p <0.05).

Conclusions: The reliable positive effect of heparizin on the disturbed parameters of the functional state of the pancreas and liver in CP in combination with CVHC was proven and allowed to assert the anti-inflammatory activity of heparizin, optimizing its effect on protein metabolism and functions of the pancreas and liver. It is recommended to additionally include the hepatotrophic agent heparizin to the protocol complex therapy of patients with chronic pancreatitis against the background of treated etiologically CVHC at the stage of outpatient rehabilitative treatment.
ЗНАЧЕННЯ ПАРАМЕТРІВ ДОБОВОГО МОНІТОРУВАННЯ АРТЕРІАЛЬНОГО ТИСКУ В ПАЦІЄНТІВ ІЗ ЦУКРОВИМ ДІАБЕТОМ 2 ТИПУ Й АРТЕРІАЛЬНОЮ ГІПЕРТЕНЗІЄЮ
Authors: Батюх О. В. , Мазур Л. П.
Published: February 2024

Важливим фактором ризику виникнення серцево-судинних захворювань вважають цукровий діабет 2 типу (ЦД 2 типу). Контроль артеріального тиску (АТ) і маси тіла є важливим елементом у системі заходів боротьби з розвитком можливих серцево-судинних ускладнень у пацієнтів із ЦД 2 типу.

Мета роботи – проаналізувати особливості добового індексу АТ, показники добового моніторування АТ у пацієнтів із ЦД 2 типу й артеріальною гіпертензією.

Основна частина. У дослідженні взяли участь 25 пацієнтів віком 39–74 роки. Обстежуваних поділили на дві групи. До 1-ї дослідної групи ввійшли 13 пацієнтів із ЦД 2 типу й артеріальною гіпертензією, з них 9 жінок віком 52–74 роки та 4 чоловіків віком 61–72 роки, до 2-ї – 12 хворих на ЦД 2 типу, з них 7 жінок віком 39–66 років і 5 чоловіків віком 41–64 роки. Для дослідження використовували монітор добового артеріального тиску «Heaco ABPM50». Інтервал вимірювання під час сну становив 60 хв, у період неспання – 30 хв. При визначенні добового індексу АТ профіль типу «дипер» виявлено в 4 обстежуваних 1-ї групи і 7 осіб 2-ї групи, профіль «нон дипер» – у 4 пацієнтів 1-ї групи та 5 хворих 2-ї групи, профілі «овер дипер» і «найт пікер» – лише у пацієнтів 1-ї групи (відповідно, 3 та 2 осіб). Середньодобові значення систолічного та діастолічного АТ у пацієнтів 1-ї групи достовірно перевищували показники хворих 2-ї групи. Середньодобовий пульс у пацієнтів 1-ї групи був дещо більший, але перебував у межах норми і становив 72,04 уд./хв, у хворих 2-ї групи – 70,44 уд./хв. Середньодобовий показник пульсового тиску в обстежуваних 1-ї групи становив 62,95 одиниці, що перевищувало допустимі межі, а в осіб 2-ї групи – 45,93 одиниці, що в межах допустимої норми.

Висновки. Аналіз показників холтерівського моніторування свідчить про значно вищі показники середньодобових значень артеріального тиску, пульсу, пульсового тиску в пацієнтів 1-ї групи (цукровий діабет 2 типу й артеріальна гіпертензія), що може бути пов’язано з рядом факторів ризику. Визначено, що моніторування параметрів артеріального тиску має прогностичне значення та дозволяє вчасно відкоригувати лікування пацієнтів з метою запобігання розвитку ускладнень.