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Total neoadjuvant therapy vs standard therapy of locally advanced rectal cancer with high-risk factors for failure

World Journal of Gastrointestinal Oncology 2021年第2期13卷 119-130页

作者： Mojca Tuta Nina Boc Erik Brecelj monika Peternel Vaneja Velenik division of Radiology Institute of OncologyLjubljana 1000Slovenia Faculty of Medicine University of LjubljanaLjubljana 1000Slovenia division of Surgery Institute of OncologyLjubljana 1000Slovenia division of Radiotherapy Institute of OncologyLjubljana 1000Slovenia

BACKGROUNd For locally advanced rectal cancer(LARC),standard therapy[consisting of neoadjuvant chemoradiotherapy(CRT),surgery,and adjuvant chemotherapy(ChT)]achieves excellent local ***,survival is still poor due to distant metastases,which remains the leading cause of death among these *** recent years,the concept of total neoadjuvant treatment(TNT)has been developed,whereby all systemic ChT-mainly affecting micrometastases-is applied prior to *** To compare standard therapy and total neoadjuvant therapy for LARC patients with high-risk factors for *** In a retrospective study,we compared LARC patients with high-risk factors for failure who were treated with standard therapy or with ***-risk for failure was defined according to the presence of at least one of the following factors:T4 stage;N2 stage;positive mesorectal fascia;extramural vascular invasion;positive lateral lymph *** consisted of 12 wk of induction ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin,CRT with capecitabine,and 6-8 wk of consolidation ChT with capecitabine and oxaliplatin or folinic acid,fluorouracil and oxaliplatin prior to *** primary endpoint was pathological complete response(pCR).In total,72 patients treated with standard therapy and 89 patients treated with TNT were included in the *** Compared to standard therapy,TNT showed a higher proportion of pCR(23%vs 7%;P=0.01),a lower neoadjuvant rectal score(median:8.43 vs 14.98;Pd N-downstaging(70%and 94%vs 51%and 86%),equivalent R0 resection(95%vs 93%),shorter time to stoma closure(mean:20 vs 33 wk;Pduring systemic ChT(completed all cycles 87%vs 76%;Pde≥3 during ChT(3%vs 14%,Pd equivalent acute toxicity and compliance during CRT and in the postoperative *** pCR rate in patients treated with TNT was significantly higher in patients

关键词： Locally advanced rectal cancer Total neoadjuvant therapy Pathological complete response Neoadjuvant rectal cancer score

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Rescue of p53 functions by in vitro-transcribed mRNA impedes the growth of high-grade serous ovarian cancer

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Cancer Communications 2024年第1期44卷 101-126页

作者： monika Raab Izabela Kostova Samuel Peña-Llopis daniela Fietz monika Kressin Seyed Mohsen Aberoumandi Evelyn Ullrich Sven Becker Mourad Sanhaji Klaus Strebhardt department of Gynecology Medical SchoolGoethe-UniversityFrankfurt am MainGermany Translational Genomics in Solid Tumors West German Cancer CenterUniversity HospitalEssenGermany German Cancer Consortium(dKTK) EssenGermany German Cancer Research Center(dKFZ) HeidelbergGermany Histology and Embryology Institute for Veterinary AnatomyGiessenGermany Franfurt Cancer Institute(FCI) Goethe UniversityFrankfurt am MainGermany German Cancer Consortium(dKTK) Partner site Frankfurt/Mainza partnership between DKFZ and University Hospital FrankfurtFrankfurt am MainGermany Experimental Immunology Department for Children and Adolescents MedicineUniversity Hospital FrankfurtGoethe UniversityFrankfurt am MainGermany

Background:The cellular tumor protein p53(TP53)is a tumor suppressor gene that is frequently mutated in human *** various cancer types,the very aggressive high-grade serous ovarian carcinoma(HGSOC)exhibits the high-est prevalence of TP53 mutations,present in>96%of *** intensive efforts to reactivate p53,no clinical drug has been approved to rescue p53 *** this study,our primary objective was to administer in vitro-transcribed(IVT)wild-type(WT)p53-mRNA to HGSOC cell lines,primary cells,and ortho-topic mouse models,with the aim of exploring its impact on inhibiting tumor growth and dissemination,both in vitro and in ***:To restore the activity of p53,WT p53 was exogenously expressed in HGSOC cell lines using a mammalian vector ***,IVT WT p53 mRNA was delivered into different HGSOC model systems(primary cells and patient-derived organoids)using liposomes and studied for proliferation,cell cycle progression,apoptosis,colony formation,and chromosomal *** alterations induced by p53 mRNA were analyzed using RNA sequencing in OVCAR-8 and primary HGSOC cells,followed by ingenuity path-way *** vivo effects on tumor growth and metastasis were studied using orthotopic xenografts and metastatic intraperitoneal mouse ***:Reactivation of the TP53 tumor suppressor gene was explored in differ-ent HGSOC model systems using newly designed IVT mRNA-based *** introduction of WT p53 mRNA triggered dose-dependent apoptosis,cell cycle arrest,and potent long-lasting inhibition of HGSOC cell *** analysis of OVCAR-8 cells upon mRNA-based p53 reactivation revealed significant alterations in gene expression related to p53 signaling,such as apoptosis,cell cycle regulation,and dNA *** p53 function concurrently reduces chromosomal instability within the HGSOC cells,under-scoring its crucial contribution in safeguarding genomic integrity by moderating the baselin

关键词： apoptosis cell cycle chromosomal instability HGSOC metastatic intraperitoneal mouse model HGSOC orthotopic Xenograft model high-grade serous ovarian cancer in vitro-transcribed p53-mRNA liposomal IVT mRNA delivery system patient-derived organoid patient-derived primary cancer cell

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Priming the tooth surface with chlorhexidine and antibacterial activity of resin cement

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World Journal of Clinical Cases 2013年第8期1卷 249-255页

作者： monika Saini Yashpal Singh Rishabh Garg Anita Pandey department of Prosthodontics Subharti Dental CollegeMeerut 250003India department of Microbiology Subharti Medical CollegeMeerut 250003India

AIM: To evaluate the effect of priming the tooth surface with 2% chlorhexidine gluconate on antibacteria activity of resin cement. METHOdS: Ten patients in whom a single missing tooth was present on both the right and left side in the upper or lower arch were selected. Two fixed partia dentures(FPds) in each patient on the right and left side were planned. Each FPd was assigned either to the control or test group. In the control group, FPd was luted with resin cement and in the test group, the tooth surface was primed with 2% chlorhexidine gluconate before luting with resin cement. Bacteriological samples were collected at base line level, as the patient came to the outpatient department before the start of any treatment, 5 wk prior to cementation of FPd and at 13 wk(8wk after final cementation). Microbiological processing of all samples was done and the results were statistically analyzed. RESULTS: In the test group, a predominance of aerobic/facultative gram positive cocci rod was seen which indicates a healthy periodontal site, whereas in thecontrol group, a predominance of anaerobic gram negative rods was present which indicates an unhealthy periodontal condition. This is evident by the fact that the anaerobic bacteria percentage in the control sample is 57% and 15% in the test sample after 13 wk, whereas the aerobic/facultative bacteria percentage is 43% in the control sample and 85% in the test sample after 13 wk. The percentage of gram negative bacteria in the control sample is 61% and in the test sample is 20% after 13 wk, whereas the percentage of gram positive bacteria in the control sample is 39% and in the test sample is 80% after 13 wk. The shift from anaerobic gram negative bacteria to aerobic gram positive bacteria is clearly seen from the control to test sample after 13 wk. CONCLUSION: The present study demonstrated that priming the tooth surface with 2% chlorhexidine gluconate may enhance antibacterial activity of the resin cement.

关键词： Fixed prosthesis Antibacterial activity Chlorhexidine Periodontitis Resin cement

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Probiotics and postbiotics in colorectal cancer:Prevention and complementary therapy

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World Journal of Gastroenterology 2022年第27期28卷 3370-3382页

作者： monika Kvakova Anna Kamlarova Jana Stofilova Veronika Benetinova Izabela Bertkova Center of Clinical and Preclinical Research MEdIPARK Faculty of MedicineP.J.Safarik University in KosiceKosice 04011Slovakia

Colorectal cancer(CRC)is a leading cause of human mortality *** conventional anticancer therapy not always being effective,there is growing interest in innovative“drug-free”cancer treatments or interventions that improve the efficacy of established *** is associated with microbiome alterations,a process known as dysbiosis that involves depletion and/or enrichment of particular gut bacterial species and their metabolic *** patient treatment with traditional probiotics(with or without prebiotics),nextgeneration probiotics(NGP),or postbiotics represents a potentially effective and accessible complementary anticancer strategy by restoring gut microbiota composition and/or by signaling to the *** this capacity,restoration of the gut microbiota in cancer patients can stabilize and enhance intestinal barrier function,as well as promote anticarcinogenic,anti-inflammatory,antimutagenic or other biologically important biochemical pathways that show high specificity towards tumor *** benefits of traditional probiotics,NGP,and postbiotics include modulating gut microbiota composition and function,as well as the host inflammatory *** application in CRC prevention is highlighted in this review,where we consider supportive in vitro,animal,and clinical *** on emerging research,NGP and postbiotics hold promise in establishing innovative treatments for CRC by conferring physiological functions via the production of dominant natural products and metabolites that provide new host-microbiota signals to combat *** favorable results have been reported,further investigations focusing on strain and dose specificity are required to ensure the efficacy and safety of traditional probiotics,NGP,and postbiotics in CRC prevention and treatment.

关键词： Colorectal cancer Traditional probiotics Next-generation probiotics Postbiotics Gut microbiota

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Combined effects of gallic acid and propolis on beryllium-induced hepatorenal toxicity

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Integrative Zoology 2008年第3期3卷 194-207页

作者： Satendra K.NIRALA Peiqiang LI monika BHAdAURIA Guangqin GUO Institute of Cell Biology School of Life SciencesLanzhou UniversityLanzhouChina Institute of Genetics School of Basic Medical SciencesLanzhou UniversityLanzhouChina National Laboratory of Applied Organic Chemistry Lanzhou UniversityLanzhouChina

The combined effect of gallic acid (3,4,5-trihydroxy benzoic acid;GA;50 mg kg^(-1) i.p.) and propolis (200 mg kg^(-1)p.o.)was evaluated against beryllium-induced biochemical and morphological alterations in the liver and kidney. Femalealbino rats were exposed to beryllium nitrate (1 mg kg^(-1)i.p.) daily for 28 days followed by treatment with the abovementioned therapeutic agents either individually or in combination for five consecutive days. Exposure to berylliumincreased its concentration in the serum, liver and kidney and caused significant alterations in cytochrome P450enzymes, microsomal lipid peroxidation and protein contents. Beryllium administration significantly altered theaspartate aminotransaminase, alanine aminotransaminase, lactate dehydrogenase, -glutamyl transpeptidase,bilirubin, creatinine and urea in serum, and the activity of acid phosphatase, alkaline phosphatase, adenosinetriphosphatase, glucose-6-phophatase and succinic dehydrogenase, triglycerides, cholesterol, protein contents,glycogen contents, lipid peroxidation and glutathione level in the liver and kidney. Beryllium exposure inducedsevere alterations in hepatorenal morphology, revealing its toxic consequences at a cellular level. Individual administrationof GA and propolis reduced the effects on the studied parameters to a degree. Interestingly, GA in conjunctionwith propolis reversed the alterations in all of the variables examined, highlighting the beneficial effects ofcombined therapy over monotherapy in the alleviation of beryllium-induced systemic toxicity.

关键词： beryllium toxicity gallic acid 3,4,5-trihydroxy benzoic acid hepatorenal dysfunction propolis

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COVId-19 survivors:Multi-disciplinary efforts in psychiatry and medical humanities for long-term realignment

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World Journal of Psychiatry 2022年第7期12卷 995-998页

作者： Henriette Löffler-Stastka monika Pietrzak-Franger department of Psychoanalysis and Psychotherapy Medical University ViennaVienna 1090Austria of English and American Studies University ViennaVienna 1090Austria

The coronavirus disease 2019 pandemic represents an enduring transformation in health care and education with the advancement of smart universities,telehealth,adaptive research protocols,personalized medicine,and self-controlled or artificial intelligence-controlled *** changes,of course,also cover mental health and long-term realignment of coronavirus disease 2019 *** or anxiety,as the most prominent psychiatric“long coronavirus disease 2019”symptoms,need a theory-based and empirically-sound procedure that would help us grasp the complexity of the condition in research and *** the systemic character of the condition,such strategies have to take the whole individual and their sociocultural context into ***,at the moment,attempts to build an integrative framework for providing meaning and understanding for the patients of how to cope with anxiety when they are confronted with empirically reduced parameters(e.g.,severe acute respiratory syndrome coronavirus type 2)or biomarkers(e.g.,the FK506 binding protein 5)are *** this context,multidisciplinary efforts are *** therefore join in a plea for an establishment of‘translational medical humanities’that would allow a more straightforward intervention of humanities(e.g.,the importance of the therapist variable,continuity,the social environment,etc)into the disciplinary,medial,political,and popular cultural debates around health,health-care provision,research(e.g.,computer scientists for simulation studies),and wellbeing.

关键词： Long COVId Resilience Multi-disciplinarity Medical Humanities Psychiatric sequelae

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The effects of 12 weeks of functional strength training on muscle strength,volume and activity upon exposure to elevated Gz forces in high-performance aircraft personnel

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Military Medical Research 2021年第4期8卷 481-489页

作者： monika Rausch Frank Weber Sven Kühn Carla Ledderhos Christoph Zinner Billy Sperlich Multinational Medical Coordination Centre/European Medical Command Andernacher Strasse 10056070 KoblenzGermany. German Air Force Center of Aerospace Medicine 82256 FuerstenfeldbruckGermany. department of Radiology Bundeswehr Central Hospital56072 KoblenzGermany. department of Sport University of Applied Sciences for Police and Administration of Hesse65199 WiesbadenGermany. Integrative&Experimental Exercise Science&Training Institute of Sport ScienceUniversity of Wuerzburg97082 WuerzburgGermany

Background:Technological advancements in modern military and acrobatic jet planes have resulted in extraordinary psychophysiological loads being exerted upon flying personnel,including inducing neck and back *** purpose of this study was to examine the effects of 12 weeks of functional strength training on 1)the volume and strength of the neck and shoulder muscles and 2)muscular activity upon exposure to helmets of different masses and elevated Gz forces in a long-arm centrifuge in high-performance aircraft ***:Eighteen participants underwent 12 weeks of functional strength training(n=12)or the control protocol(n=6)without additional strength ***-and post-intervention tests included evaluations of isometric strength of the head extensor muscles,flexion,and lateral flexion and rotation,as well as magnetic resonance imaging(MRI)to measure the volume of the ***,***,and deep neck ***,during a long-arm centrifuge(+1.4 and+3Gz)protocol,the muscular activity levels of the ***,*** and *** spinae muscles were assessed without a flight helmet,with a helmet,and with a helmet and night vision *** participant’s perception of muscular strain was noted immediately after the long-arm centrifuge ***:The maximal isometric strength in all exercises and muscle volumes increased in the training group but not the control group(Pdecreased after the intervention in the training but not the control group(P=0.01).Relative muscle activity while wearing a helmet and night vision goggles was higher after intervention in the control group than in the training group(Pd muscular strain of the neck muscles induced by the long-arm centrifuge did not differ between the ***:Twelve weeks of functional strength training improves the maximal isometric strength and volume of neck and shoulder m

关键词： Fighter pilots Long-arm centrifuge Muscular strain Strength training Neck muscle High-performance aircraft Gz forces

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Should mitral valve prolapse be considered as one of the risk factors for open angle glaucoma? A preliminary observation

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International Journal of Ophthalmology(English edition) 2022年第2期15卷 346-351页

作者： Ewa Grudzińska Malgorzata Peregud-Pogorzelska daniel Zaborski monika Modrzejewska Second department of Ophthalmology Pomeranian Medical UniversitySzczecin 70-111Poland department of Cardiology Pomeranian Medical UniversitySzczecin 70-111Poland Laboratory of Biostatistics West Pomeranian University of TechnologySzczecin 71-270Poland

AIM:To assess the incidence of mitral valve prolapse in patients with newly diagnosed primary open angle ***:The study included 12 patients without any other comorbidities or taking any general or local *** patient underwent a full ophthalmological examination with visual field assessment and optical computed tomography of the macula and optic nerve *** doppler ultrasound was performed to exclude impaired blood flow in this region and transthoracic echocardiography with assessment of the function and morphology of the heart ***:In the study group,mitral valve prolapse was found in seven patients(58.3%),while mitral valve regurgitation in 11 patients(91.7%).One case of normal pressure glaucoma and four cases of juvenile glaucoma were *** were also other risk factors for glaucoma:myopia(58.3%),migraine headaches(41.7%),a positive family history of glaucoma(16.7%).CONCLUSION:Mitral valve prolapse could be indicated as a new risk factor for *** seems reasonable to conduct screening tests for glaucoma in patients with mitral valve prolapse in the course of echocardiography.

关键词： ultrasonography doppler echocardiography heart valves mitral valve insufficiency

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Alterations in the polysialylated neural cell adhesion molecule and retinal ganglion cell density in mice with diabetic retinopathy

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International Journal of Ophthalmology(English edition) 2018年第10期11卷 1608-1615页

作者： Natalia Lobanovskaya monika Jürgenson Anu Aonurm-Helm Alexander Zharkovsky department of Pharmacology Centre of Excellence for Translational Medicine University of Tartu

AIM：To investigate the impact of polysialylated neural cell adhesion molecule（PSA-NCAM）on the survival of retinal ganglion cells（RGCs）in the experimentally induced diabetes in ***：diabetes was induced in 2.5 months old Swiss Webster mice by intraperitoneal injection of streptozotocin（STZ,90 mg/kg）once daily for two consecutive *** of the proteins of interest in the retinas from diabetic mice at 2mo after diabetes induction was performed using immunohistochemistry and Western blot *** were counted in the wholemounted retinas,and Brn3a marker was ***：Examination of retinas from diabetic mice at 2mo after diabetes induction revealed a considerable reduction in RGC *** experiments also demonstrated a redistribution of PSA-NCAM in the retina of diabetic ***-NCAM immunoreactivity was diminished in the inner part of the retina where RGCs were *** contrast,an enhanced PSA-NCAM immunoreactivity was detected in the outer layers of the ***-NCAM signal was co-localized with glial fibrillary acidic protein immunoreactivity in the Müller cell *** studies have shown that matrix metalloproteinase-9（MMP-9）is responsible for the reduction in PSA-NCAM levels in neuronal *** reduced levels of PSA-NCAM in inner layers（nerve fiber layer,ganglion cell layer）were accompanied by the increased expression of *** contrast,in the outer retinal layers,the expression of MMP-9 was much less ***：MMP-9 induces PSA-NCAM shedding in the inner part of the retina and the decreased level of PSA-NCAM in the inner part of the retina might be,at least in part,responsible for the loss of RGCs in diabetic mice.

关键词： diabetic retinopathy matrix metalloproteinase-9 polysialylated neural cell adhesion molecule retinal ganglion cells

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Phosphorus Starvation Tolerance in Rice Through Combined Physiological,Biochemical,and Proteome Analyses

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Rice science 2023年第6期30卷 613-631页

作者： Prathap V Suresh KUMAR Nand Lal MEENA Chirag MAHESHWARI monika dALAL Aruna TYAGI division of Biochemistry Indian Council of Agricultural Research-Indian Agricultural Research InstituteNew Delhi 110012India division of Germplasm Evaluation National Bureau of Plant Genetic ResourcesNew Delhi 110012India National Institute for Plant Biotechnology New Delhi 110012India

Phosphorus(P) deficiency limits the growth,development,and productivity of *** better understand the underlying mechanisms in P-deficiency tolerance and the role of Pup1 QTL in enhancing P use efficiency(PUE) for the development of P-efficient rice cultivars,a pair of contrasting rice genotypes(Pusa-44 and NIL-23) was applied to investigate the morpho-physio-biochemical and proteomic variation under P-starvation *** rice genotypes were grown hydroponically in a PusaRich medium with adequate P(16 mg/kg,+P) or without P(0 mg/kg,-P) for 30 d.P-starvation manifested a significant reductions in root and shoot biomass,shoot length,leaf area,total chlorophyll,and P,nitrogen and starch contents,as well as protein kinase *** stress increased root-to-shoot biomass ratio,root length,sucrose content,and acid phosphatase activity,particularly in the P-tolerant genotype(NIL-23).Comparative proteome analysis revealed several P metabolism-associated proteins(including OsCdPKs,OsMAPKs,OsCPKs,OsLecRK2,and OsSAPks) to be expressed in the shoot of NIL-23,indicating that multiple protein kinases were involved in P-starvation/deficiency ***,the up-regulated expression of OsrbcL,OsABCG32,OsSUS5,OsPoll-like B,and ClpC2 proteins in the shoot,and OsACA9,OsACA8,OsSPS2F,OsPP2C15,and OsBiP3 in the root of NIL-23,indicated their role in P-starvation stress control through the Pup1 QTL. Thus,our findings indicated that-P stress-responsive proteins,in conjunction with morpho-physio-biochemical modulations,improved PUE and made NIL-23 a P-deficiency tolerant genotype due to the introgression of the Pup1 QTL in the Pusa-44 background.

关键词： phosphorus deficiency Pup1 QTL protein kinase acid phosphatase proteome analysis rice

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