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synthetic lethality by PARP inhibitors: new mechanism uncovered based on unresolved transcription-replication conflicts

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signal Transduction and Targeted Therapy 2024年第8期9卷 3163-3164页

作者： marina Kolesnichenko Claus scheidereit Department of Hepatology and Gastroenterology Charite-Universitatsmedizin BerlinBerlinGermany Laboratory for signal Transduction in Tumor Cells Max Delbruck Center for Molecular Medicine in the Helmholtz Association(MDC)BerlinGermany

In a landmark study recently published in Nature,Petropoulous et *** that synthetic lethality of poly(ADP-ribose)polymerase(PARP)inhibitors in cells with defective homologous recombination repair(HR)results predominantly from transcription replication conflicts(TRC)and not,as previously proposed,from PARP trapping on DNA(Fig.1).The article unveils a new mechanism behind synthetic lethality of PARP inhibitors with relevance for cancer therapy.

关键词： al. PARP mechanism

在当前猪圆环病毒2型流行病学背景下重新审视猪圆环病毒病诊断标准

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国外畜牧学（猪与禽） 2024年第3期44卷 1-9页

作者：孟霞(译) 王祎汀(校) 夏俊花(复校) Joaquim segalés marina sibila 不详

目前,人们对猪圆环病毒2型(porcine circovirus 2,PCV2)引起的猪圆环病毒病(porcine circovirus diseases,PCVDs)的认识是,该病包括PCV2的亚临床感染(porcine circovirus 2 subclinical infection,PCV2-sI)、全身性疾病(PCV2 systemic diseases,PCV2-sD)和繁殖障碍(PCV2 reproductive diseases,PCV2-RD)以及猪皮炎肾病综合征(porcine dermatitis and nephropathy syndrome,PDNs)。多年来,确诊这些疾病的诊断标准没有变,因此,由临床症状、病变和病变组织中病毒的检测组成的三要素仍然是PCV2-sD和PCV2-RD确诊的标志。相比之下,正常情况下不对PCV2-sI进行诊断,因为这种疾病被默认通过接种疫苗就能得到控制。PDNs可以通过大体病变和组织病理学检查进行诊断,检测PCV2被认为不是该病的诊断标准。在过去十年中,分子生物学方法作为PCVDs诊断的替代方法已得到广泛使用,不过这些技术被视为监测工具,而不是诊断工具。多年来,PCV2的流行病学发生了很大的变化,由于大规模接种疫苗,猪群的感染压下降,猪群的整体免疫力降低。因此,近来来对PCVDs诊断的需求有所增加,尤其是接种疫苗后仍出现PCV2-sD症状的病例。本综述的目的是更新有关PCVDs诊断标准,并在PCV2感染的不同流行病学情况下,将分子生物学方法应用于这些疾病的整体诊断中。

关键词：猪圆环病毒2型猪圆环病毒病临床症状病理学诊断流行病学

Immune signature of small bowel adenocarcinoma and the role of tumor microenvironment

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World Journal of Gastroenterology 2024年第8期30卷 794-798页

作者： Grigorios christodoulidis marina Nektaria Kouliou Konstantinos Eleftherios Koumarelas Department of General surgery University Hospital of LarissaLarissa 41110Greece

In this editorial we comment on the article published“Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment”.small bowel adenocarcinoma(sBA)is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area,sBA accounts for less than 3%of such *** detection is challenging and the reason arises from its asymptomatic nature,often leading to late-stage discovery and poor *** involves platinum-based chemotherapy with a 5-fluorouracil combination,but the lack of effective chemotherapy contributes to a generally poor *** are linked to genetic disorders and risk factors,including chronic inflammatory *** unique characteristics of the small bowel,such as rapid cell renewal and an active immune system,contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable *** cell death-ligand 1(PD-L1)expression varies across different cancers,with potential discrepancies in its prognostic *** instability(MsI)in sBA is associated with a high tumor mutational burden,affecting the prognosis and response to *** presence of PD-L1 and programmed cell death 1,along with tumor-infiltrating lymphocytes,plays a crucial role in the complex microenvironment of sBA and contributes to a more favorable prognosis,especially in the context of high MsI *** tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MsI status and a favorable prognosis,emphasizes the importance of evaluating the immune status of tumors for treatment decisions.

关键词： Programmed cell death 1 Programmed cell death-ligand 1 Programmed death ligand small bowel adenocarcinoma Tumor infiltrating lymphocytes Tumor microenvironment Microsatellite instability

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1578-1595页

作者： Eric Toshiyuki Nakamura Amanda Park marina Alessandra Pereira Daniel Kikawa Francisco Tustumi Department of Gastroenterology Instituto do CâncerHospital das Clínicas da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of scientific Initiation Universidade Mogi das CruzesSão Paulo 08780911Brazil Department of Evidence-Based Medicine Centro Universitário LusíadaCentre for Evidence-Based MedicineCentro Universitário Lusíada(UNILUS)SantosBrazil Department of surgery Hospital Israelita Albert EinsteinSão Paulo 05652900Brazil

BACKGROUND Heat shock proteins(HsPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many *** prognostic significance of HsPs and their regulatory factors,such as heat shock factor 1(HsF1)and CHIP,are poorly *** To investigate the relationship between HsP expression and prognosis in esophageal and esophagogastric *** A systematic review was conducted in accordance with PRIsMA recommend-ations(PROsPERO:CRD42022370653),on Embase,PubMed,Cochrane,and ***,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were ***-positive patients were compared with HsP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(Os).HsPs were stratified according to the HsP family,and the summary risk difference(RD)was calculated using a random-effect *** The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 ***40 and 60 were associated with a higher 3-year Os[HsP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HsP60:RD=0.33;95%CI:0.17-0.50],while HsF1 was associated with a poor 3-year Os(RD=-0.22;95%CI:-0.32 to-0.12).The other HsP families were not associated with long-term ***1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HsP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HsP families was not significantly related to tumor depth and lymph node or distant *** The expression levels of certain families of HsP,such as HsP40 and 60 and HsF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

关键词： Heat-shock proteins Heat-shock response Prognosis Esophageal neoplasms Meta-analysis

Use of infrared thermography to detect reactions to stressful events:does animal personality matter?

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Integrative Zoology 2024年第2期19卷 224-239页

作者： Maria Vittoria MAZZAMUTO marina MORANDINI William LAMPMAN Lucas Armand WAUTERs Damiano PREATONI John Lad KOPROWsKI Adriano MARTINOLI school of Natural Resources and Environment College of Agriculture and Life ScienceUniversity of ArizonaArizonaUSA Unitàdi Analisi e Gestione delle Risorse Ambientali Dipartimento di Scienze Teoriche e ApplicateGuido Tosi Research GroupUniversitàdegli Studi dell’InsubriaVareseItaly Haub school of Environment and Natural Resources University of WyomingWyomingUSA

The study of the relationship between animal stress and personality for free-ranging animals is limited and provides contrasting *** perception of stressors by an individual may vary due to its personality,and certain personality traits may help individuals to better cope with *** non-invasive infrared thermography(IRT),we investigated the link between physiological and behavioral components expressed during an acute stress event by free-ranging Fremont’s squirrels(Tamiasciurus fremonti).We expected that,during the acute stress event of being approached by the researcher,individuals that showed a fast pace-of-life syndrome(bolder,more active,and less social/more aggressive)based on an arena test would exhibit stronger sympathetic-adrenal-medullary system reactivity showing a more intense stress-induced hyperthermia(high core body temperature and low peripheral temperature)than individuals with a slow pace of life(shy,less active,and more social).We successfully employed IRT technology to images of Fremont’s squirrels with identification of the individuals’body parts(eye,nose,ear,hind foot).However,we found no support for our ***’body surface temperatures told us more about a squirrel’s external environment and less about the thermal state of the body in that environment following a stressful *** studies need to assess how to make IRT effective and efficient in the field and improve its performance in studying the relationships between physiology and personality in wildlife.

关键词： non-invasive method open field test physiology stress-induced hyperthermia Tamiasciurus fremonti

There is more to the knee joint than just the quadriceps:A systematic review with meta-analysis and evidence gap map of hamstring strength,flexibility,and morphology in individuals with gradual-onset knee disorders

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Journal of sport and Health science 2024年第4期13卷 521-536页

作者： Helder s.Lopes marina C.Waiteman Liliam B.Priore Neal R.Glaviano David M.Bazett-Jones Ronaldo V.Briani Fabio M.Azevedo school of science and Technology Physical Therapy DepartmentSao Paulo State University(UNESP)Presidente Prudente 19060-900Brazil Department of Kinesiology College of AgricultureHealth and Natural ResourcesUniversity of ConnecticutStorrsCT 06269USA school of Exercise and Rehabilitation sciences College of Health and Human ServicesUniversity of ToledoToledoOH 43606USA

Background:Impairments in hamstring strength,flexibility,and morphology have been associated with altered knee biomechanics,pain,and *** the presence of these impairments in individuals with gradual-onset knee disorders is important and may indicate targets for assessment and *** systematic review aimed to synthesize the literature to determine the presence of impairments in hamstring strength,flexibility,and morphology in individuals with gradual-onset knee ***:Five databases(MEDLINE,Embase,CINAHL,sPORTDiscus,and Web of science)were searched from inception to september *** studies comparing hamstring outcomes(e.g.,strength,flexibility,and/or morphology)between individuals with gradual-onset knee disorders and their unaffected limbs or pain-free controls were ***-analyses for each knee disorder were ***-level certainty was assessed using the Grading of Recommendations Assessment,Development,and Evaluation,and evidence gap maps were ***:seventy-nine studies across 4 different gradual-onset knee disorders(i.e.,knee osteoarthritis(OA),patellofemoral pain(PFP),chondromalacia patellae,and patellar tendinopathy)were *** with knee OA presented with reduced hamstring strength compared to pain-free controls during isometric(standard mean difference(sMD)=-0.76,95%confidence interval(95%CI):-1.32 to-0.21)and concentric contractions(sMD=-0.97,95%CI:-1.49 to-0.45).Individuals with PFP presented with reduced hamstring strength compared to painfree controls during isometric(sMD=-0.48,95%CI:-0.82 to-0.14),concentric(sMD=-1.07,95%CI:-2.08 to-0.06),and eccentric contractions(sMD=-0.59,95%CI:-0.97 to-0.21).No differences were observed in individuals with patellar *** with PFP presented with reduced hamstring flexibility when compared to pain-free controls(sMD=-0.76,95%CI:-1.15 to-0.36).Evidence gap maps identified insufficient evidence for chondromalacia patel

关键词： Chondromalacia patellae Knee flexors Knee osteoarthritis Patellar tendinopathy Patellofemoral pain

May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients’questions?An evidencecontrolled analysis

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World Journal of Gastroenterology 2024年第1期30卷 17-33页

作者： Antonietta Gerarda Gravina Raffaele Pellegrino marina Cipullo Giovanna Palladino Giuseppe Imperio Andrea Ventura salvatore Auletta Paola Ciamarra Alessandro Federico Division of Hepatogastroenterology Department of Precision MedicineUniversity of Campania Luigi VanvitelliNaples 80138Italy

Artificial intelligence is increasingly entering everyday *** language model(LLM)systems such as Chat Generative Pre-trained Transformer(ChatGPT)have become potentially accessible to everyone,including patients with inflammatory bowel diseases(IBD).However,significant ethical issues and pitfalls exist in innovative LLM *** hype generated by such systems may lead to unweighted patient trust in these ***,it is necessary to understand whether LLMs(trendy ones,such as ChatGPT)can produce plausible medical information(MI)for *** review examined ChatGPT’s potential to provide MI regarding questions commonly addressed by patients with IBD to their *** the review of the outputs provided by ChatGPT,this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some *** studies and refinement of the ChatGPT,possibly aligning the outputs with the leading medical evidence provided by reliable databases,are needed.

关键词： Crohn’s disease Ulcerative colitis Inflammatory bowel disease Chat Generative Pre-trained Transformer Large language model Artificial intelligence

*** model of riboflavin transporter deficiency(RTD)disorder reveals deficits in synaptic transmission and movement

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Genes & Diseases 2024年第4期11卷 120-123页

作者： Ramesh K.Narayanan Gonzalo Perez-siles Kamila A.Marzec Alexandra Boyling Brent Neumann Manoj P.Menezes marina L.Kennerson Northcott Neuroscience Laboratory ANZAC Research Institute-Sydney Local Health DistrictSydneyNSW 2139Australia sydney Medical school University of SydneySydneyNSw 2050Australia ANZAC Research Institute-sydney Local Health District SydneyNSW 2139Australia Neuroscience Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVictoria 3800Australia TY Nelson Department of Neurology and Neurosurgery and Kids Neuroscience Children's Hospital at WestmeadWestmeadSydneyNSW2145Australia Paediatrics and Child Health The University of SydneySydneySydneyNSW 2145Australia Molecular Medicine Laboratory Concord General Repatriation HospitalSydneyNSW 2139Australia

Riboflavin transporter deficiency(RTD),previously known as Brown-Vialetto-Van Laere syndrome,is a childhoodonset neurodegenerative disorder characterized by sensory and motor neuron degeneration causing ataxia,muscle weakness,optic atrophy,and respiratory *** in sLC52A2 and sLC52A3,solute carrier family members that encode riboflavin(RF)transporters RFVT2 and RFVT3,are known to cause RTD types 2 and 3,respectively.

关键词： RTD degeneration TD

跨媒介表征:论亚历山大·格林小说中的文学图像

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广东开放大学学报 2024年第2期33卷 64-69页

作者：布哈罗娃·玛丽娜天津师范大学天津300382

俄国白银时代重要作家亚历山大·格林在其小说中擅用绘画元素呈现浪漫主义的艺术审美,绘画成为小说文本的媒介呈现。拥有良好艺术功底的格林惯常以绘画作为介质实现小说文本的艺术追求,通过“文学图像”的活现,格林小说中语像和图像“... 详细信息

俄国白银时代重要作家亚历山大·格林在其小说中擅用绘画元素呈现浪漫主义的艺术审美,绘画成为小说文本的媒介呈现。拥有良好艺术功底的格林惯常以绘画作为介质实现小说文本的艺术追求,通过“文学图像”的活现,格林小说中语像和图像“以图言说”“语图互仿”与“语图互文”的动态关系呈现,使得小说人物塑造得更为丰满,推动了小说情节叙事,打通了文本空间与现实空间的桎梏,促使人们通过观赏感受到艺术再现以及艺术与现实之间的融合。亚历山大·格林以绘画植入小说文本,实现了跨媒介、跨文本的融合,从而形成了其创作的独特性。

关键词：亚历山大·格林文学图像绘画框架艺术再现