Psoriasis is a potentially debilitating inflammatory dermatosis affecting 0.2%-4.8% of the population worldwide causing a significant occupational, personal or psychosocial morbidity to these patients for life. The ba...Psoriasis is a potentially debilitating inflammatory dermatosis affecting 0.2%-4.8% of the population worldwide causing a significant occupational, personal or psychosocial morbidity to these patients for life. The basic aim of psoriasis therapy is to control the disease to maximum possible extent and improve the patient's quality of life. Management of triggers for flareups, lifestyle modifications, and dietary supplements are often recommended. Intermittent or rotational therapy with frequent alterations in treatment options is usually needed to reduce toxicity of anti-psoriatic drugs in the absence of safer alternatives. Currently, several biological agents categorized as either T-cell targeted(e.g., Alefacept, Efalizumab) or cytokine modulating(e.g., Adalimumab, Infliximab, Etanercept) are available for treating severe psoriasis. However, their high cost is often precluding for most patients. The usefulness of systemic(methotrexate, cyclosporine, acitretin or several other therapeutic agents) or topical(tar, anthralin, corticosteroids or calcipotriol ointments, phototherapy with or without psoralens) therapies has been well established for the management of psoriasis. The literature is also replete with benefits of less used non-standard and unconventional treatment modalities(hydroxycarbamide, azathioprine, leflunomide, mycophenolate mofetil, isotretinoin, fumarates, topical calcineurin inhibitors, peroxisome proliferator-activated receptors agonists, statins, sulfasalazine, pentoxifylline, colchicine, grenz ray therapy, excimer laser, climatotherapy and balneophototherapy, peritoneal dialysis, tonsillectomy, ichthyotherapy, etc.). These can be used alternatively to treat psoriasis patients who have mild/minimal lesions, are intolerant to conventional drugs, have developed side effects or achieved recommended cumulative dose, where comorbidities pose unusual therapeutic challenges, or may be as intermittent, rotational or combination treatment alternatives.展开更多
Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.展开更多
Artificial intelligence(AI),encompassing machine learning and deep learning,is being extensively used in medical sciences.It is slated to positively impact the diagnosis and prognostication of various diseases.Deep le...Artificial intelligence(AI),encompassing machine learning and deep learning,is being extensively used in medical sciences.It is slated to positively impact the diagnosis and prognostication of various diseases.Deep learning,a subset of AI,has been instrumental in diagnosing diabetic retinopathy(DR),diabetic macular edema,glaucoma,age-related macular degeneration,and numerous other ocular diseases.AI performs equally well in the early prediction of glaucoma and agerelated macular degeneration.Integrating AI with telemedicine promises to improve healthcare delivery,although challenges persist in implementing AI algorithms,especially in deve-loping countries.This review provides a compre hensive summary of AI,its applications in ophthalmology,particularly DR,the diverse algorithms utilized for different ocular conditions,and prospects for the future integration of AI in eye care.展开更多
BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in comp...BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.展开更多
The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their recept...The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.展开更多
Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are ex...Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.展开更多
Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a...Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.展开更多
AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygiu...AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.展开更多
Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,r...Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.展开更多
The integration of Artificial Intelligence(AI)and Machine Learning(ML)into groundwater exploration and water resources management has emerged as a transformative approach to addressing global water challenges.This rev...The integration of Artificial Intelligence(AI)and Machine Learning(ML)into groundwater exploration and water resources management has emerged as a transformative approach to addressing global water challenges.This review explores key AI and ML concepts,methodologies,and their applications in hydrology,focusing on groundwater potential mapping,water quality prediction,and groundwater level forecasting.It discusses various data acquisition techniques,including remote sensing,geospatial analysis,and geophysical surveys,alongside preprocessing methods that are essential for enhancing model accuracy.The study highlights AI-driven solutions in water distribution,allocation optimization,and realtime resource management.Despite their advantages,the application of AI and ML in water sciences faces several challenges,including data scarcity,model reliability,and the integration of these tools with traditional water management systems.Ethical and regulatory concerns also demand careful consideration.The paper also outlines future research directions,emphasizing the need for improved data collection,interpretable models,real-time monitoring capabilities,and interdisciplinary collaboration.By leveraging AI and ML advancements,the water sector can enhance decision-making,optimize resource distribution,and support the development of sustainable water management strategies.展开更多
Today we live in a world of Hydrocarbon Energy Carriers, where Carbon is always used as a Carrier for Hydrogen 1) Biomass (CH1.44O0.66 or C6H12O6);2) Natural Gas [NG] (CH4);3) Water Gas [C+H2O];4) Gasoline (C6H12, C7H...Today we live in a world of Hydrocarbon Energy Carriers, where Carbon is always used as a Carrier for Hydrogen 1) Biomass (CH1.44O0.66 or C6H12O6);2) Natural Gas [NG] (CH4);3) Water Gas [C+H2O];4) Gasoline (C6H12, C7H18, C8H18, etc.);5) Kerosene (C17H36, C18H38, C19H40, C20H42, C21H44, C22H46, etc.) and;6) Crude Oil. The Carbon aggregates are all storable and have worthwhile, logistically manageable energy densities. But whenever recovering Energy from the Carbon molarities, CO2 gets emitted into the atmosphere, while separate use of Hydrogen Energy contents carried by the Carbon moieties would just generate water vapor. Hydrogen is also the most important intermediary in Refineries, hydrogenating lower grade Hydrocarbons into higher potencies, or for removing Sulfur by the formation of Hydrogen Sulfur, that can be dissociated after its segregation from the Hydrocarbon products. But most of the internal Hydrogen yields in Refineries today is used for onsite production of Ammonia as a basis for Energy fertilizers in high performance agriculture. Because Hydrogen is awkward to store and transport, most of it is currently used captive within large size centralized plants as a reactant for producing Hydrocarbon energy carriers, using the Carbon as a carrier for the Hydrogen moieties, to then be distributed over big enough areas for consumption of the such large scale plants’ volumes. With recently proven achievements of Hydrogen production from excess Wind & Solar Power by electrolysis, Hydrogen could become available in abundant quantities, to be distributed locally within the coverage area of the transmission grid such Wind & Solar installations are feeding into. In combination with Carbon as a reactant such abundant Hydrogen could also be synthesized into Hydrocarbon Energy Carriers and substitute fossil commodities.展开更多
Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly devel...Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.展开更多
Starting from Wigner’s definition of the function named now after him we systematically develop different representation of this quasiprobability with emphasis on symmetric representations concerning the canonical va...Starting from Wigner’s definition of the function named now after him we systematically develop different representation of this quasiprobability with emphasis on symmetric representations concerning the canonical variables (q,p) of phase space and using the known relation to the parity operator. One of the representations is by means of the Laguerre 2D polynomials which is particularly effective in quantum optics. For the coherent states we show that their Fourier transforms are again coherent states. We calculate the Wigner quasiprobability to the eigenstates of a particle in a square well with infinitely high impenetrable walls which is not smooth in the spatial coordinate and vanishes outside the wall boundaries. It is not well suited for the calculation of expectation values. A great place takes on the calculation of the Wigner quasiprobability for coherent phase states in quantum optics which is essentially new. We show that an unorthodox entire function plays there a role in most formulae which makes all calculations difficult. The Wigner quasiprobability for coherent phase states is calculated and graphically represented but due to the involved unorthodox function it may be considered only as illustration and is not suited for the calculation of expectation values. By another approach via the number representation of the states and using the recently developed summation formula by means of Generalized Eulerian numbers it becomes possible to calculate in approximations with good convergence the basic expectation values, in particular, the basic uncertainties which are additionally represented in graphics. Both considered examples, the square well and the coherent phase states, belong to systems with SU (1,1) symmetry with the same index K=1/2 of unitary irreducible representations.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as L...Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.展开更多
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential ...Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 9 more questions are presented as followed. Question 67. How could we overcome the resistance of hepatocellular carcinoma against chemotherapeutics? Question 68. Is pursuit of non-covalent small-molecule binders of RAS proteins viable as a strategy of cancer drug discovery? Question 69. In what oligomeric structures do RAS proteins signal? Question 70. How can we achieve non-invasive early detection and diagnosis of lung cancer? Question 71. Does genetic information influence the volatolome enabling diagnosis of lung cancer with genetic mutations via cell headspace or breath analysis? Question 72. Is heavy ion beam radiotherapy e ective to kill cancer stem cells? Question 73. Is there any diversity among di erent types of cancer in terms of sensitivity to heavy ion beam radiotherapy? Question 74. Can targeted alpha-particle therapy augment the e ect of carbon ion radiotherapy on malignancies? Question 75. How does chromosomal instability drive tumor progression?展开更多
N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis a...N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.展开更多
Promotion is an essential element in the marketing mix. It is used by businesses to inform, influence and persuade customers to adopt the products and services they offer. Without promotion, business would be stagnant...Promotion is an essential element in the marketing mix. It is used by businesses to inform, influence and persuade customers to adopt the products and services they offer. Without promotion, business would be stagnant and lack substantial growth because the brands would have low visibility in the market. Moreover, today’s vast and assorted markets comprise of customers with different needs and varied behavior. So it is rarely possible for companies to satisfy all customers by treating them alike. Thus there arises a need to divide the market into segments having customers with similar traits/characteristics. After identifying appropriate market segments, firms can design differentiated promotional campaigns for each segment. At the same time there can be a mass market promotional campaign that reaches different segments with a fixed spectrum. Also since promotional effort resources are limited, one must use them judiciously. In this paper, we formulate mathematical programming problem under repeat purchase scenario, which optimally allocates mass promotional effort resources and differentiated promotional effort resources across the segments dynamically in order to maximize the overall sales obtained from multiple products of a product line under budgetary and minimum sales aspiration level constraint on each product under consideration in each segment. The planning horizon is divided into multi periods, the adoption pattern of each product in each segment is observed in every subinterval and accordingly promotional effort allocations are determined for the next period till we reach the end of planning period. The optimization model has been further extended to incorporate minimum aspiration level constraints on total sales for each product under consideration from all the segments taken together. The non linear programming problem so formulated is solved using differential evolution approach. A numerical example has been discussed to illustrate applicability of the model.展开更多
Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograf...Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograft biopsies are not suitable for continuous monitoring of rejection.Thus,there is an unmet need for non-invasive methods to diagnose acute and chronic rejection.Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003.This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses.The potential limitations and open questions in establishing proteomic markers for rejection are discussed,including ongoing trials and future challenges to this topic.展开更多
文摘Psoriasis is a potentially debilitating inflammatory dermatosis affecting 0.2%-4.8% of the population worldwide causing a significant occupational, personal or psychosocial morbidity to these patients for life. The basic aim of psoriasis therapy is to control the disease to maximum possible extent and improve the patient's quality of life. Management of triggers for flareups, lifestyle modifications, and dietary supplements are often recommended. Intermittent or rotational therapy with frequent alterations in treatment options is usually needed to reduce toxicity of anti-psoriatic drugs in the absence of safer alternatives. Currently, several biological agents categorized as either T-cell targeted(e.g., Alefacept, Efalizumab) or cytokine modulating(e.g., Adalimumab, Infliximab, Etanercept) are available for treating severe psoriasis. However, their high cost is often precluding for most patients. The usefulness of systemic(methotrexate, cyclosporine, acitretin or several other therapeutic agents) or topical(tar, anthralin, corticosteroids or calcipotriol ointments, phototherapy with or without psoralens) therapies has been well established for the management of psoriasis. The literature is also replete with benefits of less used non-standard and unconventional treatment modalities(hydroxycarbamide, azathioprine, leflunomide, mycophenolate mofetil, isotretinoin, fumarates, topical calcineurin inhibitors, peroxisome proliferator-activated receptors agonists, statins, sulfasalazine, pentoxifylline, colchicine, grenz ray therapy, excimer laser, climatotherapy and balneophototherapy, peritoneal dialysis, tonsillectomy, ichthyotherapy, etc.). These can be used alternatively to treat psoriasis patients who have mild/minimal lesions, are intolerant to conventional drugs, have developed side effects or achieved recommended cumulative dose, where comorbidities pose unusual therapeutic challenges, or may be as intermittent, rotational or combination treatment alternatives.
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
文摘Artificial intelligence(AI),encompassing machine learning and deep learning,is being extensively used in medical sciences.It is slated to positively impact the diagnosis and prognostication of various diseases.Deep learning,a subset of AI,has been instrumental in diagnosing diabetic retinopathy(DR),diabetic macular edema,glaucoma,age-related macular degeneration,and numerous other ocular diseases.AI performs equally well in the early prediction of glaucoma and agerelated macular degeneration.Integrating AI with telemedicine promises to improve healthcare delivery,although challenges persist in implementing AI algorithms,especially in deve-loping countries.This review provides a compre hensive summary of AI,its applications in ophthalmology,particularly DR,the diverse algorithms utilized for different ocular conditions,and prospects for the future integration of AI in eye care.
文摘BACKGROUND Complement-mediated thrombotic microangiopathy(TMA)is a rare endothelial injury syndrome caused by dysregulated activation of the alternative complement pathway,often linked to genetic abnormalities in complement factor H(CFH),complement factor I,or complement factor H-related(CFHR)proteins.Both renal transplantation and pregnancy are independent triggers for recurrence.This case highlights a genetically high-risk patient who achieved a successful term pregnancy after renal transplantation without complement inhibition,emphasizing individualized risk stratification,close surveillance,and multidisciplinary management for favourable maternal and graft outcomes.CASE SUMMARY A 32-year-old woman with end-stage renal disease secondary to genetically confirmed complement-mediated TMA—homozygous CFH exon 17 deletion and CFHR3-CFHR1 duplication—was maintained on dialysis for 2.5 years before undergoing a successful live-donor kidney transplant from her mother.Post-transplant immunosuppression included tacrolimus,mycophenolate mofetil,and prednisolone,later modified to azathioprine during pregnancy planning.One-year post-transplant,she conceived spontaneously.Pregnancy was complicated by transient gestational hypertension,controlled with nifedipine,labetalol,and amlodipine.Proteinuria remained<150 mg/day;white blood cell counts 5.8-7.2×109/L without cytopenia.Serum creatinine ranged 0.9-1.1 mg/dL,and tacrolimus trough levels 5-7 ng/mL.At 36 weeks,she delivered a healthy 3 kg infant by elective caesarean section.Postpartum follow-up at three months confirmed stable maternal and graft function.CONCLUSION High-risk complement-mediated TMA patients can achieve successful pregnancy post-transplant through individualized care without mandatory complement blockade.
基金supported by JSPS(KAKENHI:21K06205,23K06937,24K23419)AMED(to JYK,SaY,TM,SiY,YT,and NH)JYW had long been supported by the NIH.
文摘The nervous system processes a vast amount of information,performing computations that underlie perception,cognition,and behavior.During development,neuronal guidance genes,which encode extracellular cues,their receptors,and downstream signal transducers,organize neural wiring to generate the complex architecture of the nervous system.It is now evident that many of these neuroguidance cues and their receptors are active during development and are also expressed in the adult nervous system.This suggests that neuronal guidance pathways are critical not only for neural wiring but also for ongoing function and maintenance of the mature nervous system.Supporting this view,these pathways continue to regulate synaptic connectivity,plasticity,and remodeling,and overall brain homeostasis throughout adulthood.Genetic and transcriptomic analyses have further revealed many neuronal guidance genes to be associated with a wide range of neurodegenerative and neuropsychiatric disorders.Although the precise mechanisms by which aberrant neuronal guidance signaling drives the pathogenesis of these diseases remain to be clarified,emerging evidence points to several common themes,including dysfunction in neurons,microglia,astrocytes,and endothelial cells,along with dysregulation of neuron-microglia-astrocyte,neuroimmune,and neurovascular interactions.In this review,we explore recent advances in understanding the molecular and cellular mechanisms by which aberrant neuronal guidance signaling contributes to disease pathogenesis through altered cell-cell interactions.For instance,recent studies have unveiled two distinct semaphorin-plexin signaling pathways that affect microglial activation and neuroinflammation.We discuss the challenges ahead,along with the therapeutic potentials of targeting neuronal guidance pathways for treating neurodegenerative diseases.Particular focus is placed on how neuronal guidance mechanisms control neuron-glia and neuroimmune interactions and modulate microglial function under physiological and pathological conditions.Specifically,we examine the crosstalk between neuronal guidance signaling and TREM2,a master regulator of microglial function,in the context of pathogenic protein aggregates.It is well-established that age is a major risk factor for neurodegeneration.Future research should address how aging and neuronal guidance signaling interact to influence an individual’s susceptibility to various late-onset neurological diseases and how the progression of these diseases could be therapeutically blocked by targeting neuronal guidance pathways.
文摘Colorectal cancer (CRC) is an important health issue in Taiwan. There were over ten thousand newly diagnosed CRC patients each year. The outcome of late stage CRC still remains to be improved, and tumor markers are expected to improve CRC detection and management. From a colorectal cancer cell secretome database, we chose four proteins as candidates for clinical verification, including tumor-associated calcium signal transducer 2 (TROP2, TACSTD2), transmembrane 9 superfamily member 2 (TM9SF2), and tetraspanin-6 (TSPAN6), and tumor necrosis factor receptor superfamily member 16 (NGFR). Different groups of 30 CRC patients’ tissue samples collected from Chang Gung Memorial Hospital were analyzed by immunohistochemistry (IHC) for the four proteins, and the results were scored by pathologist. For all the four candidate proteins, marked differences of IHC score existed between tumor and adjacent non-tumor counterpart. However, there were only trends between higher protein expression levels and worse outcome. Three proteins (TROP2, TM9SF2 and NGFR) had trends between higher tissue expression and tumor stage or lymph node metastasis. Our study revealed that tissue expression of four proteins (TROP2, TM9SF2, TSPAN6, and NGFR) was markedly different between tumor and adjacent non-tumor counterparts. Overexpression of all these four proteins showed some trends with poorer survival.
基金supported by grants from the Deutsche Forschungsgemeinschaft(DFG)to MW.
文摘Oligodendrocytes and their cell-intrinsic gene regulatory network:Oligodendrocytes(OLs)are the myelinating glial cells of the vertebrate central nervous system.They are responsible for insulating neuronal axons with a lipid-rich myelin sheath,which enables the saltatory conduction of action potentials.During development,oligodendrocyte progenitor cells(OPCs)emerge from neural stem cells in the ventricular zone.They then proliferate,increase their number,and migrate to their final destination where they encounter unmyelinated neuronal axons and differentiate in a stepwise fashion into myelinating oligodendrocytes(mOLs)under the influence of environmental stimuli.
文摘AIM:To investigate the effect of pentagonal conjunctival autograft on reducing graft retraction following pterygium surgery.METHODS:This retrospective comparative study included patients who underwent primary pterygium excision with either pentagonal(created by shaping the junction with the recipient conjunctiva into a wedge)or quadrangular conjunctival autograft transplantation.All patients completed a 6mo postoperative follow-up.The primary outcome measure was the incidence of graft retraction;secondary outcomes included graft displacement requiring re-suturing and pterygium recurrence rate.RESULTS:The study enrolled 58 participants,comprising 26(15 males,11 females)in the pentagonal graft group(mean age:54.9±13.1y),and 32(17 males,15 females)in the quadrangular graft group(mean age:57.6±10.4y).Graft retraction occurred in only 1 eye(3.8%)in the pentagonal autograft group,compared to 9 eyes(28.1%)in the quadrangular autograft group.No cases of graft displacement requiring re-suturing were reported in the pentagonal autograft group.Although graft displacement and recurrence requiring re-suturing were observed less frequently in surgeries with a pentagonal graft,the difference was not statistically significant(P>0.05).CONCLUSION:Designing the conjunctival autograft in a pentagonal shape—mimicking geodesic dome architecture and conforming to the eye’s spherical structure—enhances compatibility with the recipient conjunctiva and improves resistance to physical traction forces.This design effectively reduces the incidence of graft retraction and other related complications,providing a more favorable surgical option for pterygium treatment.
文摘Kidney transplantation(KT)accounts for nearly three-fourths of organ transplants in India,with living donors contributing to 82%of cases.Induction immunosuppression is essential to optimize initial immunosuppression,reduce acute rejections,and enable tailored use of maintenance agents.Rabbit anti-thymocyte globulin(rATG)and interleukin-2 receptor anatagonists(IL-2RA/IL-2RBs)are the most widely used induction therapies.However,data on induction practices across India are limited.To evaluate induction immunosuppression practices across KT centers in India and establish a consensus for different subsets of KT recipients.A nationwide online survey was conducted by the Indian Society of Organ Transplantation(ISOT)among its members(400 KT centers).Responses were analyzed to assess induction practices across diverse donor types,age groups,and immunological risk profiles.Heterogeneity in practices prompted consensus building using a modified Delphi process.Literature review and expert panel discussions(April 2024)were followed by structured voting,and 16 consensus statements were finalized.Of 400 centers approached,254 participated.rATG was the most commonly used induction therapy,followed by IL-2RBs;alemtuzumab was least used.Significant heterogeneity was observed in type,dose,and duration of induction therapy.Consensus recommendations were framed:rATG for high immunological risk recipients and deceased donor KTs;IL-2RB or low-dose rATG for low immunological risk;rituximab in ABOincompatible KTs;and tailoring based on age,diabetes,donor type,infection risk,and affordability.This first ISOT consensus provides 16 India-specific statements on induction therapy in KT.It emphasizes risk-stratified,evidenceinformed,and context-appropriate induction strategies,supporting standardization of care across the country.
文摘The integration of Artificial Intelligence(AI)and Machine Learning(ML)into groundwater exploration and water resources management has emerged as a transformative approach to addressing global water challenges.This review explores key AI and ML concepts,methodologies,and their applications in hydrology,focusing on groundwater potential mapping,water quality prediction,and groundwater level forecasting.It discusses various data acquisition techniques,including remote sensing,geospatial analysis,and geophysical surveys,alongside preprocessing methods that are essential for enhancing model accuracy.The study highlights AI-driven solutions in water distribution,allocation optimization,and realtime resource management.Despite their advantages,the application of AI and ML in water sciences faces several challenges,including data scarcity,model reliability,and the integration of these tools with traditional water management systems.Ethical and regulatory concerns also demand careful consideration.The paper also outlines future research directions,emphasizing the need for improved data collection,interpretable models,real-time monitoring capabilities,and interdisciplinary collaboration.By leveraging AI and ML advancements,the water sector can enhance decision-making,optimize resource distribution,and support the development of sustainable water management strategies.
文摘Today we live in a world of Hydrocarbon Energy Carriers, where Carbon is always used as a Carrier for Hydrogen 1) Biomass (CH1.44O0.66 or C6H12O6);2) Natural Gas [NG] (CH4);3) Water Gas [C+H2O];4) Gasoline (C6H12, C7H18, C8H18, etc.);5) Kerosene (C17H36, C18H38, C19H40, C20H42, C21H44, C22H46, etc.) and;6) Crude Oil. The Carbon aggregates are all storable and have worthwhile, logistically manageable energy densities. But whenever recovering Energy from the Carbon molarities, CO2 gets emitted into the atmosphere, while separate use of Hydrogen Energy contents carried by the Carbon moieties would just generate water vapor. Hydrogen is also the most important intermediary in Refineries, hydrogenating lower grade Hydrocarbons into higher potencies, or for removing Sulfur by the formation of Hydrogen Sulfur, that can be dissociated after its segregation from the Hydrocarbon products. But most of the internal Hydrogen yields in Refineries today is used for onsite production of Ammonia as a basis for Energy fertilizers in high performance agriculture. Because Hydrogen is awkward to store and transport, most of it is currently used captive within large size centralized plants as a reactant for producing Hydrocarbon energy carriers, using the Carbon as a carrier for the Hydrogen moieties, to then be distributed over big enough areas for consumption of the such large scale plants’ volumes. With recently proven achievements of Hydrogen production from excess Wind & Solar Power by electrolysis, Hydrogen could become available in abundant quantities, to be distributed locally within the coverage area of the transmission grid such Wind & Solar installations are feeding into. In combination with Carbon as a reactant such abundant Hydrogen could also be synthesized into Hydrocarbon Energy Carriers and substitute fossil commodities.
文摘Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.
文摘Starting from Wigner’s definition of the function named now after him we systematically develop different representation of this quasiprobability with emphasis on symmetric representations concerning the canonical variables (q,p) of phase space and using the known relation to the parity operator. One of the representations is by means of the Laguerre 2D polynomials which is particularly effective in quantum optics. For the coherent states we show that their Fourier transforms are again coherent states. We calculate the Wigner quasiprobability to the eigenstates of a particle in a square well with infinitely high impenetrable walls which is not smooth in the spatial coordinate and vanishes outside the wall boundaries. It is not well suited for the calculation of expectation values. A great place takes on the calculation of the Wigner quasiprobability for coherent phase states in quantum optics which is essentially new. We show that an unorthodox entire function plays there a role in most formulae which makes all calculations difficult. The Wigner quasiprobability for coherent phase states is calculated and graphically represented but due to the involved unorthodox function it may be considered only as illustration and is not suited for the calculation of expectation values. By another approach via the number representation of the states and using the recently developed summation formula by means of Generalized Eulerian numbers it becomes possible to calculate in approximations with good convergence the basic expectation values, in particular, the basic uncertainties which are additionally represented in graphics. Both considered examples, the square well and the coherent phase states, belong to systems with SU (1,1) symmetry with the same index K=1/2 of unitary irreducible representations.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
文摘Artificial intelligence(AI)-augmented contrast-enhanced ultrasonography(CEUS)is emerging as a powerful tool in liver imaging,particularly in enhancing the accuracy of Liver Imaging Reporting and Data System(known as LI-RADS)classi-fication.This review synthesized published data on the integration of machine learning and deep learning techniques into CEUS,revealing that AI algorithms can improve the detection and quantification of contrast enhancement patterns.Such improvements led to more consistent LI-RADS categorization,reduced interoperator variability,and enabled real-time analysis that streamlined work-flow.The enhanced sensitivity of AI tools facilitated better differentiation between benign and malignant lesions,ultimately optimizing patient management.These advances suggest that AI-augmented CEUS could transform liver imaging by providing rapid,reliable,and objective assessments.However,the review also highlighted the need for further large-scale,multicenter studies to fully validate these findings and ensure the safe integration of AI into routine clinical practice.INTRODUCTION International hepatology society guidelines have established contrast-enhanced computed tomography(CT)and contrast-enhanced magnetic resonance imaging(MRI)as the imaging modalities of choice for diagnosing hepatocellular carcinoma(HCC)lesions larger than 1 cm.MRI remains the gold standard for detecting small HCC nodules in cirrhotic livers due to its superior soft-tissue contrast and functional imaging capabilities.However,early or atypical presentations remain challenging for differential diagnosis,staging,and treatment planning.In these scenarios contrast-enhanced ultrasonography(CEUS)is a valuable second-line tool,offering real-time,radiation-free evaluation and repeatability for follow-up.A recent meta-analysis of head-to-head studies reported comparable diagnostic performance between CEUS and CT/MRI with pooled sensitivities and specificities of 0.67/0.88 for CEUS vs 0.60/0.98 for CT/MRI in non-HCC malignancies,and similar specificities for HCC diagnosis(0.70 for CEUS vs 0.59 for CT;0.81 for CEUS vs 0.79 for MRI)[1].Given the limitations of individual imaging modalities,hybrid techniques and multimodal approaches are gaining traction for improving lesion detection,especially in cases where standard methods fall short.Artificial intelligence(AI)has emerged as a powerful tool in medical imaging,enhancing diagnostic accuracy and reliability across platforms.In CEUS liver imaging dynamic enhancement patterns often challenge consistent interpretation across observers.AI holds particular promise for standardizing assessments.The growing complexity of liver tumor evaluation has also driven interest in approaches that integrate serum bio-markers with advanced imaging.However,no single strategy currently meets all the diagnostic and prognostic re-quirements.Recent studies highlighted the potential of AI to bridge this gap by enabling precise image interpretation and facilitating the integration of heterogeneous clinical and imaging data[2].Altogether the convergence of CEUS with AI and radiomics offers a dynamic,quantitative,and potentially reproducible paradigm for liver lesion assessment,comple-menting traditional imaging methods.This review aimed to provide an overview of current advances in AI-driven CEUS for liver lesion assessment with a particular focus on automated Liver Imaging Reporting and Data System(LI-RADS)classification,radiomics-based models,and future clinical integration.While another recent systematic review[3]provided a comprehensive analysis of AI applications in CEUS,our approach offers a targeted perspective,emphasizing LI-RADS-centered scoring,automated lesion characterization,and clinical utility,particularly in the context of HCC diagnosis and management.In the methodological process of this narrative mini-review,the literature selection was primarily based on targeted PubMed searches.ChatGPT-4o(OpenAI)[4]was employed to assist in refining query parameters and identifying relevant,up-to-date peer-reviewed sources on CEUS-based AI applications.
文摘Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology, which sparkle diverse thoughts, interesting communications, and potential collaborations among researchers all over the world. In this article, 9 more questions are presented as followed. Question 67. How could we overcome the resistance of hepatocellular carcinoma against chemotherapeutics? Question 68. Is pursuit of non-covalent small-molecule binders of RAS proteins viable as a strategy of cancer drug discovery? Question 69. In what oligomeric structures do RAS proteins signal? Question 70. How can we achieve non-invasive early detection and diagnosis of lung cancer? Question 71. Does genetic information influence the volatolome enabling diagnosis of lung cancer with genetic mutations via cell headspace or breath analysis? Question 72. Is heavy ion beam radiotherapy e ective to kill cancer stem cells? Question 73. Is there any diversity among di erent types of cancer in terms of sensitivity to heavy ion beam radiotherapy? Question 74. Can targeted alpha-particle therapy augment the e ect of carbon ion radiotherapy on malignancies? Question 75. How does chromosomal instability drive tumor progression?
基金supported by the Natural Science Foundation of Heilongjiang Province of China,Outstanding Youth Foundation,No.YQ2022H003 (to DW)。
文摘N6-methyladenosine(m^(6)A), the most prevalent and conserved RNA modification in eukaryotic cells, profoundly influences virtually all aspects of mRNA metabolism. mRNA plays crucial roles in neural stem cell genesis and neural regeneration, where it is highly concentrated and actively involved in these processes. Changes in m^(6)A modification levels and the expression levels of related enzymatic proteins can lead to neurological dysfunction and contribute to the development of neurological diseases. Furthermore, the proliferation and differentiation of neural stem cells, as well as nerve regeneration, are intimately linked to memory function and neurodegenerative diseases. This paper presents a comprehensive review of the roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, as well as its implications in memory and neurodegenerative diseases. m^(6)A has demonstrated divergent effects on the proliferation and differentiation of neural stem cells. These observed contradictions may arise from the time-specific nature of m^(6)A and its differential impact on neural stem cells across various stages of development. Similarly, the diverse effects of m^(6)A on distinct types of memory could be attributed to the involvement of specific brain regions in memory formation and recall. Inconsistencies in m^(6)A levels across different models of neurodegenerative disease, particularly Alzheimer's disease and Parkinson's disease, suggest that these disparities are linked to variations in the affected brain regions. Notably, the opposing changes in m^(6)A levels observed in Parkinson's disease models exposed to manganese compared to normal Parkinson's disease models further underscore the complexity of m^(6)A's role in neurodegenerative processes. The roles of m^(6)A in neural stem cell proliferation, differentiation, and self-renewal, and its implications in memory and neurodegenerative diseases, appear contradictory. These inconsistencies may be attributed to the timespecific nature of m^(6)A and its varying effects on distinct brain regions and in different environments.
文摘Promotion is an essential element in the marketing mix. It is used by businesses to inform, influence and persuade customers to adopt the products and services they offer. Without promotion, business would be stagnant and lack substantial growth because the brands would have low visibility in the market. Moreover, today’s vast and assorted markets comprise of customers with different needs and varied behavior. So it is rarely possible for companies to satisfy all customers by treating them alike. Thus there arises a need to divide the market into segments having customers with similar traits/characteristics. After identifying appropriate market segments, firms can design differentiated promotional campaigns for each segment. At the same time there can be a mass market promotional campaign that reaches different segments with a fixed spectrum. Also since promotional effort resources are limited, one must use them judiciously. In this paper, we formulate mathematical programming problem under repeat purchase scenario, which optimally allocates mass promotional effort resources and differentiated promotional effort resources across the segments dynamically in order to maximize the overall sales obtained from multiple products of a product line under budgetary and minimum sales aspiration level constraint on each product under consideration in each segment. The planning horizon is divided into multi periods, the adoption pattern of each product in each segment is observed in every subinterval and accordingly promotional effort allocations are determined for the next period till we reach the end of planning period. The optimization model has been further extended to incorporate minimum aspiration level constraints on total sales for each product under consideration from all the segments taken together. The non linear programming problem so formulated is solved using differential evolution approach. A numerical example has been discussed to illustrate applicability of the model.
基金Supported by The Deutsche Forschungsgemeinschaft,No.GW 4/6-1
文摘Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients.Reliable and timely diagnosis is important to treat rejection as early as possible.Allograft biopsies are not suitable for continuous monitoring of rejection.Thus,there is an unmet need for non-invasive methods to diagnose acute and chronic rejection.Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003.This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses.The potential limitations and open questions in establishing proteomic markers for rejection are discussed,including ongoing trials and future challenges to this topic.
