Risk of hepatitis B virus reactivation in oncological patients treated with tyrosine kinase inhibitors:A case report and literature analysis

Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.

Soft,body conformable electronics for thermoregulation enabled by kirigami

The application of thermoelectric devices(TEDs)for personalized thermoregulation is attractive for saving energy while balancing the quality of life.TEDs that directly attach to human skin remarkably minimized the energy wasted for cooling the entire environment.However,facing the extreme dynamic geometry change and strain of human skin,conventional TEDs cannot align with the contour of our bodies for the best thermoregulation effect.Hence,we designed a kirigami-based wearable TED with excellent water vapor permeability,flexibility,and conformability.Numerical analysis and experimental results reveal that our product can withstand various types of large mechanical deformation without circuit rupture.The stated outcome and proposed facile approach not only reinforce the development of wearable TEDs but also offer an innovative opportunity for different electronics that require high conformability.

ELK3-ID4 axis governs the metastatic features of triple negative breast cancer

Purpose:Cancer cell metastasis is a multistep process,and the mechanism underlying extravasation remains unclear.ELK3 is a transcription factor that plays a crucial role in regulating various cellular processes,including cancer metastasis.Based on the finding that ELK3 promotes the metastasis of triple-negative breast cancer(TNBC),we investigated whether ELK3 regulates the extravasation of TNBC by forming the ELK3-ID4 axis.ID4 functions as a transcriptional regulator that interacts with other transcription factors,inhibiting their activity and subsequently influencing various biological processes associated with cell differentiation,survival,growth,and metastasis.Methods:We assessed the correlation between the expression of ELK3 and that of ID4 in TNBCs using bioinformatics analyses,QRT-PCR,western blot analysis,luciferase reporter assays,and chromatin immunoprecipitation.Migration,adhesion,invasion,and lung metastasis assays were employed to determine whether the ELK3-ID4 axis regulates the metastatic features of TNBC.Results:We found that ELK3 binds directly to a binding motif close to the ID4 promoter to repress promoter activity.The expression of E-cadherin in TNBC was regulated by the ELK3-ID4 axis.In vitro and in vivo analyses showed that inhibiting ID4 expression in ELK3-knockdown MDA-MB-231(ELK3KD)cells restored the ability to extravasate and metastasize.Conclusion:The results indicate that the ELK3 regulates ID4 promoter activity,and that the ELK3-ID4 axis regulates the metastatic characteristics of TNBC cells.Additionally,the data suggest that the ELK3-ID4 axis regulates metastasis of TNBCs by modulating expression of E-cadherin.

Potential applications of 7 Tesla magnetic resonance imaging in paediatric neuroimaging:Feasibility and challenges

The integration of 7 Tesla magnetic resonance imaging(7 T MRI)in adult patients has marked a revolutionary stride in radiology.In this article we explore the feasibility of 7 T MRI in paediatric practice,emphasizing its feasibility,applications,challenges,and safety considerations.The heightened resolution and tissue contrast of 7 T MRI offer unprecedented diagnostic accuracy,particularly in neuroimaging.Applications range from neuro-oncology to neonatal brain imaging,showcasing its efficacy in detecting subtle structural abnormalities and providing enhanced insights into neurological conditions.Despite the promise,challenges such as high cost,discomfort,and safety concerns necessitate careful consideration.Research suggests that,with precautions,7 T MRI is feasible in paediatrics,yet ongoing studies and safety assessments are imperative.

Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans:an overview of recent findings

Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.

Lower limb suspension induces threshold-specific alterations of motor units properties that are reversed by active recovery

Purpose:This study aimed to non-invasively test the hypothesis that(a) short-term lower limb unloading would induce changes in the neural control of force production(based on motor units(MUs) properties) in the vastus lateralis muscle and(b) possible changes are reversed by active recovery(AR).Methods:Ten young males underwent 10 days of unilateral lower limb suspension(ULLS) followed by 21 days of AR.During ULLS,participants walked exclusively on crutches with the dominant leg suspended in a slightly flexed position(15°-20°) and with the contralateral foot raised by an elevated shoe.The AR was based on resistance exercise(leg press and leg extension) and executed at 70% of each participant’s 1repetition maximum,3 times/week.Maximal voluntary isometric contraction(MVC) of knee extensors and MUs properties of the vastus lateralis muscle were measured at baseline,after ULLS,and after AR.MUs were identified using high-density electromyography during trapezoidal isometric contractions at 10%,25%,and 50% of the current MVC,and individual MUs were tracked across the 3 data collection points.Results:We identified 1428 unique MUs,and 270 of them(18.9%) were accurately tracked.After ULLS,MVC decreased by 29.77%,MUs absolute recruitment/derecruitment thresholds were reduced at all contraction intensities(with changes between the 2 variables strongly correlated),while discharge rate was reduced at 10% and 25% but not at 50% MVC.Impaired MVC and MUs properties fully recovered to baseline levels after AR.Similar changes were observed in the pool of total as well as tracked MUs.Conclusion:Our novel results demonstrate,non-invasively,that 10 days of ULLS affected neural control predominantly by altering the discharge rate of lower-threshold but not of higher-threshold MUs,suggesting a preferential impact of disuse on motoneurons with a lower depolarization threshold.However,after 21 days of AR,the impaired MUs properties were fully restored to baseline levels,highlighting the plasticity of the components involved in neural control.

Impact of increasing one-carbon metabolites on traumatic brain injury outcome using pre-clinical models

Traumatic brain injury is a major cause of death and disability worldwide,affecting over 69 million individuals yearly.One-carbon metabolism has been shown to have beneficial effects after brain damage,such as ischemic stroke.However,whether increasing one-carbon metabolite vitamins impacts traumatic brain injury outcomes in patients requires more investigation.The aim of this review is to evaluate how one-carbon metabolites impact outcomes after the onset of traumatic brain injury.PubMed,Web of Science,and Google Scholar databases were searched for studies that examined the impact of B-vitamin supplementation on traumatic brain injury outcomes.The search terms included combinations of the following words:traumatic brain injury,dietary supplementation,one-carbon metabolism,and B-vitamins.The focus of each literature search was basic science data.The year of publication in the literature searches was not limited.Our analysis of the literature has shown that dietary supplementation of B-vitamins has significantly improved the functional and behavioral recove ry of animals with traumatic brain injury compared to controls.Howeve r,this improvement is dosage-dependent and is contingent upon the onset of supplementation and whether there is a sustained or continuous delive ry of vitamin supplementation post-traumatic brain injury.The details of supplementation post-traumatic brain injury need to be further investigated.Overall,we conclude that B-vitamin supplementation improves behavioral outcomes and reduces cognitive impairment post-traumatic brain injury in animal model systems.Further investigation in a clinical setting should be stro ngly considered in co njunction with current medical treatments for traumatic brain injury-affected individuals.

Morphological,phylogenetic and metabolite profile of Prorocentrum clipeus,a newly recorded epiphytic dinoflagellate in the northern Yellow Sea

More than 30 species of benthic Prorocentrum have been identified,some of which produce okadaic acid(OA)and its derivatives,dinophysistoxins(DTXs),which cause diarrhetic shellfish poisoning(DSP).Increasing numbers of benthic Prorocentrum species have been reported in tropical and subtropical waters of China.In contrast,only a few benthic Prorocentrum species have been reported in temperate waters.In this study,morphological descriptions obtained using light microscopy,scanning electron microscopy and molecular characterization of one Prorocentrum clipeus strain isolated from the Yellow Sea are presented.Prorocentrum clipeus cells were nearly circular in shape,with a collar,ridge,and one protrusion.The periflagellar area was wide U-shaped,with two curved projections on platelet 1a.Nine periflagellar platelets of different sizes were observed.The morphology closely fits that of the species isolated from other locations.Phylogenetic analysis based on the molecular sequences of the small subunit(SSU)rDNA,internal transcribed spacer(ITS),and large subunit(LSU)rDNA was performed.A comprehensive metabolomic analysis incorporating target,suspect and non-target screenings was first applied to investigate the intracellular and extracellular metabolite profiles of the current isolate of P.clipeus.According to the results of the target and suspect screenings,179 metabolites or toxins produced by DSP-related algal species,including OA,dinophysistoxin-1(DTX1),dinophysistoxin-2(DTX2)and pectenotoxin-2(PTX2),were not detected.Non-target screening involving feature-based molecular networking(FBMN)provided a global view of major metabolites produced by the P.clipeus DF128 strain and revealed 23 clusters belonging to at least 13 compound classes,with organometallic compounds,lipids and lipid-like molecules,phenylpropanoids and polyketides,and benzenoids as major types.To date,this is the first record of the characterization of P.clipeus in samples from Chinese waters.Our results support the wide distribution of epibenthic Prorocentrum species.

Conformational dynamics as an intrinsic determinant of prion protein misfolding and neurotoxicity

The prion protein(PrP) is the key molecular and pathological mediator of prion diseases,a heterogeneous group of brain disorders with fatal outcomes.Prion diseases are rare but deserve special attention because of their unique familial,sporadic,and transmissible etiologies,all caused by a single agent:misfolded conformations of PrP.

Genetic diversity of the S-type small subunit ribosomal RNA gene of Plasmodium knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia

Objective:To determine the genetic diversity of Plasmodium(P.)knowlesi isolates from Sabah,Malaysian Borneo and Peninsular Malaysia,targeting the S-type SSU rRNA gene and including aspects of natural selection and haplotype.Methods:Thirty-nine blood samples infected with P.knowlesi were collected in Sabah,Malaysian Borneo and Peninsular Malaysia.The S-type SSU rRNA gene was amplified using polymerase chain reaction,cloned into a vector,and sequenced.The natural selection and haplotype of the S-type SSU rRNA gene sequences were determined using DnaSP v6 and illustrated using NETWORK v10.This study's 39 S-type SSU rRNA sequences and eight sequences from the Genbank database were subjected to phylogenetic analysis using MEGA 11.Results:Overall,the phylogenetic analysis showed no evidence of a geographical cluster of P.knowlesi isolates from different areas in Malaysia based on the S-type SSU rRNA gene sequences.The S-type SSU rRNA gene sequences were relatively conserved and with a purifying effect.Haplotype sharing of the S-type SSU rRNA gene was observed between the P.knowlesi isolates in Sabah,Malaysian Borneo,but not between Sabah,Malaysian Borneo and Peninsular Malaysia.Conclusions:This study suggests that the S-type SSU rRNA gene of P.knowlesi isolates in Sabah,Malaysian Borneo,and Peninsular Malaysia has fewer polymorphic sites,representing the conservation of the gene.These features make the S-type SSU rRNA gene suitable for comparative studies,such as determining the evolutionary relationships and common ancestry among P.knowlesi species.

Intraoperative cholangio-ultrasonography(IOCUS)during hepatectomy with resection of the biliary confluence:An effective alternative to intraoperative cholangiography

Intraoperative ultrasonography(IOUS)in hepatobiliary surgery is well known as an essential tool for radical and safe hepatectomies,allowing to perform parenchymal sparing surgery and,as consequence,to expand the surgical indications for patients otherwise considered unresectable.Nevertheless,since many years,despite its effectiveness in the study of vascular anatomy of the liver,the gold standard for the assessment of biliary anatomy during surgery is intraoperative cholangiography(IOC),which is used for the validation of preoperative imaging as well as for guiding reconstruction in case of bile duct injury or resection.

Occurrence of K1 and K2 serotypes and genotypic characteristics of extended spectrumβ-lactamases-producing Klebsiella pneumoniae isolated from selected hospitals in Malaysia

Objective:To determine the distribution,phenotypic and genetic background of extended spectrumβ-lactamases(ESBL)-producing Klebsiella(K.)pneumoniae clinical isolates associated with K1 and K2 serotypes in two selected hospitals in Malaysia.Methods:A total of 192 K.pneumoniae isolates were collected and subjected to antibiotic susceptibility,hypermucoviscosity test and multiplex PCR to detect the presence of K1-and K2-serotype associated genes.Multilocus sequence typing(MLST)was performed on ESBL-producing K.pneumoniae isolates presented with K1 and K2 serotypes,followed by phylogenetic analysis.Results:A total of 87 out of 192(45.3%)of the K.pneumoniae isolates collected were ESBL producers.However,only 8.3%(16/192)and 10.9%(21/192)of the total isolates were detected to carry K1-and K2-serotype associated genes,respectively.Statistical analysis showed that K1 and K2 capsular serotypes were not significantly associated with ESBL phenotype(P=0.196).However,they were significantly associated with hypervirulent,as demonstrated by the positive string test(P<0.001).MLST analysis revealed that ST23 as the predominant sequence type(ST)in the K1 serotype,while the ST in the K2 serotype is more diverse.Conclusions:Although the occurrence of ESBL-producing isolates among the hypervirulent strains was low,their coexistence warrants the need for continuous surveillance.MLST showed that these isolates were genetically heterogeneous.

Effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness:A multi-country cluster randomized controlled trial

Purpose:To examine the effects of a school-based karate intervention on academic achievement,psychosocial functioning,and physical fitness in children aged 7-8 years.Methods:Twenty schools in 5 different European countries(2 second-grade classrooms per school)participated in a cluster randomized controlled trial(Sport at School trial).Participants were assigned to either a control group,which continued with their habitual physical education lessons,or to an intervention group,which replaced these lessons with a 1-year karate intervention(Karate Mind and Movement program).A total of 721 children(344 girls and 377 boys,7.4±0.5 years old,mean±SD)completed the study,of which 333 and 388 were assigned to the control group and intervention group,respectively.Outcomes included academic performance(average grade),psychosocial functioning(Strengths and Difficulties Questionnaire for parents),and different markers of physical fitness(cardiorespiratory fitness,balance,and flexibility).Results:The intervention provided small but significant benefits compared to the control group for academic achievement(d=0.16;p=0.003),conduct problems(d=-0.28;p=0.003),cardiorespiratory fitness(d=0.36;p<0.001),and balance(d=0.24;p=0.015).There was a trend towards significant benefits for flexibility(d=0.24;p=0.056).No significant benefits were observed for other variables,including psychosocial difficulties,emotional symptoms,hyperactivity/inattention,peer problems,or prosocial behaviour(all p>0.05).Conclusion:A 1-year school-based karate intervention was effective in improving academic achievement,conduct problems,and physical fitness in primary school children.The results support the inclusion of karate during physical education lessons.

Exploring the landscape of minimally invasive pancreatic surgery: Progress, challenges, and future directions

Minimally invasive surgery(MI)has become the standard of care for many surgical procedures aimed at reducing the burden on patients.However,its adoption in pancreatic surgery(PS)has been limited by the pancreas’s unique location and the complexity of the dissection and reconstruction phases.These factors continue to contribute to PS having one of the highest morbidity and mortality rates in general surgery.Despite a rough start,MIPS has gained widespread acceptance in clinical practice recently.Robust evidence supports MI distal pancreatectomy safety,even in oncological cases,indicating its potential superiority over open surgery.However,definitive evidence of MI pancre-aticoduodenectomy(MIPD)feasibility and safety,particularly for malignant lesions,is still lacking.Nonetheless,reports from high-volume centers are emer-ging,suggesting outcomes comparable to those of the open approach.The robotic PS increasing adoption,facilitated by the wider availability of robotic platforms,may further facilitate the transition to MIPD by overcoming the technical con-straints associated with laparoscopy and accelerating the learning curve.Alth-ough the MIPS implementation process cannot be stopped in this evolving world,ensuring patient safety through strict outcome monitoring is critical.Investing in younger surgeons with structured and recognized training programs can promote safe expansion.

Influence of aging,mitochondrial dysfunction,and inflammation on Parkinson's disease

Aging is associated with chronic form of inflammation called inflammaging,which results from immune system changes.Inflammaging plays a crucial role in the pathogenesis of various neurodegenerative diseases(Dabravolski et al.,2022).Moreove r,aging-related inflammation can be triggered by disrupted mitophagy.

Weight gain after 35 years of age is associated with increased breast cancer risk: findings from a large prospective cohort study

Adiposity affects lifetime estrogen exposure,which is a key factor in breast carcinogenesis.However,adiposity effects,often assessed as the body mass index(BMI),on pre-and post-menopausal breast cancer risk are paradoxical.Body weight gain may reflect body fat mass accumulation during adulthood better than the BMI,potentially representing age-related metabolic changes.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus infection.Methods:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),respectively.In addition,the HSI was less predictive for Fibroscan®-defined fatty liver.Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and FLI.Conclusions:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty liver.In addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

PGLYRP1 protein as a novel mediator of cellular dialogue in neuroinflammation

Neuroinflammation has been identified as a crucial element in several neurological disorders. Glial cells play a critical role in directing neuroinflammation, both in deleterious and beneficial ways.

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 bleeding.Conclusions: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

The incre asing interest in RNA modifications has signifcantly advanced epigenomic and epitranscriptomic technologies.This study focuses on the immuno oncological impact of ALYREF in human cancer through a pan-cancer analysis,enhancing understanding of this gene's role in cancer.We observed differential ALYREF expression between tumor and normal samples,correl ating strongly with prognosis in various cancers,particularly kidney renal papillary cell carcinoma(KIRP)and liver hepatocellular carcinoma(LIHC).ALYREF showed a negative correlation with most tumor-infitrating cells in lung squamous cell carcinoma(LUSC)and lymphoid neoplasm difuse large B-cell lymphoma(DLBC),while positive correlations were noted in IIHC,kidney chromophobe(KICH),mesothelioma(MESO),KIRP,pheochromocytoma and paraganglioma(PARD),and glioma(GBMLGG).Aditionally,ALYREF expression was closely associated with tumor heterogeneity,stemness indices,and a high mutation rate in TP53 across these cancers.In conclusion,ALYREF may serve as an oncogenic biomarker in numerous cancers,meriting further research attention.