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The PI3K/Akt/m TOR pathway in ovarian cancer: therapeutic opportunities and challenges

Chinese Journal of Cancer 2015年第1期34卷 4-16页

作者： Bianca Cheaib Aurélie Auguste alexandra leary Gynecological Unit Department of MedicineGustave Roussy Comprehensive Cancer Centre Gynecological Tumor Team Translational Research Laboratory U981 Gustave Roussy Comprehensive Cancer Centre

The phosphatidylinositol 3 kinase(PI3K) pathway is frequently altered in cancer, including ovarian cancer(OC). Unfortunately, despite a sound biological rationale and encouraging activity in preclinical models, trials of first-generation inhibitors of mammalian target of rapamycin(m TOR) in OC have demonstrated negative results. The lack of patient selection as well as resistance to selective m TOR complex-1(m TORC1) inhibitors could explain the disappointing results thus far. Nonetheless, a number of novel agents are being investigated, including dual m TORC1/m TORC2, Akt, and PI3 K inhibitors. Although it is likely that inhibition of the PI3K/Akt/m TOR pathway may have little effect in unselected OC patients, certain histological types, such as clear cell or endometrioid OC with frequent phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit alpha(PIK3CA) and/or phosphatase and tensin homolog(PTEN) alterations, may be particularly suited to this approach. Given the complexity and redundancy of the PI3 K signaling network, PI3 K pathway inhibition may be most useful in combination with either chemotherapy or other targeted therapies, such as MEK inhibitors, anti-angiogenic therapy, and hormonal therapy, in appropriately selected OC patients. Here, we discuss the relevance of the PI3 K pathway in OC and provide an up-to-date review of clinical trials of novel PI3 K inhibitors alone or in combination with cytotoxics and novel therapies in OC. In addition, the challenges of drug resistance and predictive biomarkers are addressed.

关键词： mTOR 信号通路卵巢癌磷脂酰肌醇3激酶 AKT 激素疗法治疗临床试验

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Elevation transition of aquatic insects closely matches a thermal feature in the Yungas of Northwestern Argentina

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Journal of Mountain Science 2024年第2期21卷 433-448页

作者： alexandra BUITRAGO-GUACANAME Carlos MOLINERI Andrés LIRA-NORIEGA Daniel Andrés DOS SANTOS Neotropical Biodiversity Institute(CONICET-UNT) UNT-DomesHorco Molle S/N4107 TucumánArgentina CONACYT Research Fellow Network of Advanced Molecular StudiesInstitute of Ecology A.COld Road to Coatepec 351El HayaCP 91073XalapaVeracruzMexico Biostatistics Chair Faculty of Natural Sciences and IMLNational University of TucumánSan Miguel de TucumánMiguel Lillo 2054000 TucumánArgentina

Temperature is a key factor that shapes the distribution of *** knowledge about how species respond to temperature is relevant to devise strategies for addressing the impacts of climate *** insects are particularly vulnerable to climate change,yet there is still much to learn about their ecology and *** the Yungas ecoregion of Northwestern Argentina,cold-and warm-adapted species of the orders Ephemeroptera,Plecoptera,and Trichoptera(EPT)are segregated by *** modeled the ecological niche of South American EPT species in this region using available data and projected their potential distribution in geographic *** were grouped based on their ecogeographic similarity,and we analyzed their replacement pattern along elevation gradients,focusing on the ecotone where opposing thermal preferences *** this interface,we identified critical points where the combined incidence of cold and warm assemblages maximizes,indicating a significant transition *** found that the Montane Cloud Forest holds the interface,with a particularly greater suitability at its lower *** main axis of the interface runs in a N-S direction and falls between 14°C-16°C mean annual *** probability of a particular location within a basin being classified as part of the interface increases as Kira’s warmth index approaches a score around *** the interface is critical for defining the thermal limits of species distribution and designing biomonitoring *** in the location of thermal constants related to mountainous ecotones may cause vertical displacement of aquatic insects and vegetation *** have recognized significant temperature thresholds that serve as indicators of suitability for the *** global warming is anticipated to shift these indicators,we suggest using them to monitor the imprints of climate change on mountain ecosystems.

关键词： Austral Yungas Ecological Niche Model Ephemeroptera Kira’s warmth index Plecoptera Trichoptera

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Development and characterization of 3D-printed electroconductive pHEMA-co-MAA NP-laden hydrogels for tissue engineering

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Bio-Design and Manufacturing 2024年第3期7卷 262-276页

作者： Sara De Nitto Aleksandra Serafin alexandra Karadimou Achim Schmalenberger John J.EMulvihill Maurice N.Collins DIBRIS Polytechnic Inter-School Section University of Genoa16126 GenoaItaly School of Engineering Bernal InstituteUniversity of LimerickLimerick V94 T9PXIreland School of Natural Sciences Department of Biological SciencesUniversity of LimerickLimerick V94 T9PXIreland Health Research Institute University of LimerickLimerick V94 T9PXIreland AMBER University of LimerickLimerick V94 T9PXIreland

Tissue engineering(TE)continues to be widely explored as a potential solution to meet critical clinical needs for diseased tissue replacement and tissue *** this study,we developed a poly(2-hydroxyethyl methacrylate-co-methacrylic acid)(pHEMA-co-MAA)based hydrogel loaded with newly synthesized conductive poly(3,4-ethylene-dioxythiophene)(PEDOT)and polypyrrole(PPy)nanoparticles(NPs),and subsequently processed these hydrogels into tissue engineered constructs via three-dimensional(3D)*** presence of the NPs was critical as they altered the rheological properties during ***,all samples exhibited suitable shear thinning properties,allowing for the development of an optimized processing window for 3D *** were 3D printed into pre-determined disk-shaped configurations of 2 and 10 mm in height and diameter,*** observed that the NPs disrupted the gel crosslinking efficiencies,leading to shorter degradation times and compressive mechanical properties ranging between 450 and 550 *** conductivity of the printed hydrogels increased along with the NP concentration to(5.10±0.37)×10^(−7)S/*** vitro studies with cortical astrocyte cell cultures demonstrated that exposure to the pHEMA-co-MAA NP hydrogels yielded high cellular viability and proliferation ***,hydrogel antimicrobial studies with staphylococcus epidermidis bacteria revealed that the developed hydrogels affected bacterial *** together,these materials show promise for various TE strategies.

关键词： Conductive nanoparticles Hydroxyethyl methacrylate(HEMA) Ultraviolet(UV)polymerization 3D printing

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Rational molecular design of efficient yellow-red dendrimer TADF for solution-processed OLEDs: a combined effect of substitution position and strength of the donors

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Science China Chemistry 2024年第5期67卷 1613-1623页

作者： Changfeng Si Dianming Sun Tomas Matulaitis David B.Cordes alexandra M.Z.Slawin Eli Zysman-Colman Organic Semiconductor Centre EaStCHEM School of ChemistryUniversity of St AndrewsSt AndrewsKY169STUK

The development of high-performance solution-processed red organic light-emitting diodes(OLEDs) remains a challenge,particularly in terms of maintaining efficiency at high luminance. Here, we designed and synthesized four novel orange-red thermally activated delayed fluorescence(TADF) dendrimers that are solution-processable: 2GCz BP, 2DPACz BP, 2FBP2GCz and 2FBP2DPACz. We systematically investigated the effect of substitution position and strength of donors on the optoelectronic properties. The reverse intersystem crossing rate constant(kRISC) of the emitters having donors substituted at positions 11and 12 of the dibenzo[a,c]phenazine(BP) is more than 10-times faster than that of compounds substituted having donors substituted at positions 3 and 6. Compound 2DPACz BP, containing stronger donors than 2GCz BP, exhibits a red-shifted emission and smaller singlet-triplet energy splitting, ΔE_(ST), of 0.01 e V. The solution-processed OLED with 10 wt% 2DPACz BP doped in m CP emitted at 640 nm and showed a maximum external quantum efficiency(EQE_(max)) of 7.8%, which was effectively maintained out to a luminance of 1,000 cd m-2. Such a device's performance at relevant display luminance is among the highest for solution-processed red TADF OLEDs. The efficiency of the devices was improved significantly by using 4Cz IPN as an assistant dopant in a hyperfluorescence(HF) configuration, where the 2DPACz BP HF device shows an EQEmaxof 20.0% at λEL of 605 nm and remains high at 11.8% at a luminance of 1,000 cd m-2, which makes this device one of the highest efficiency orange-to-red HF SP-OLEDs to date.

关键词： thermally activated delayed fluorescence solution-processing red OLEDs dibenzo[a,c]phenazine dendrimers

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Biopsychosocial Review of Eating Disorders

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Open Journal of Psychiatry 2024年第2期14卷 107-119页

作者： Elizabeth Esbenshade alexandra Venegas Independent Researcher San Marino CA USA

Eating disorders are among the deadliest mental illnesses known to occur. Eating disorders directly cause 10,200 deaths each year, which is one death every 52 minutes. About 9% of the global population is affected by eating disorders at some point during their lifetime. This paper aims to provide a better understanding of the factors that contribute to the onset of eating disorders. Specifically, we examine biological factors, such as genetics, family history and the neuroscience behind eating disorders;furthermore, we explore psychological factors including other mental health conditions and their correlation, personality traits and behavioral risk factors;lastly, we consider social factors related to the onset of eating disorders, such as childhood and social environment, the media, and demographic factors.

关键词： Eating Disorders Risk Factors Etiology

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Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy alexandra Kovar Teresa S Jones Krzysztof J Wikiel Edward L Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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Motivations for and barriers to innovation in non-profit organizations: The case of nursing homes in Northern Portugal

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International Journal of Innovation Studies 2024年第1期8卷 25-44页

作者： Ana Rita Gonçalves Lopes Aldina Isabel de Azevedo Correia alexandra Maria da Silva Braga Center for Research and Innovation in Business Sciences and Information Systems School of Management and TechnologyPolitecnico do PortoRua do Curral-Margaride4610-156 FelgueirasPortugal

To contribute to the empirical literature on innovation in non-profit organizations,this study examines innovation in Private Social Solidarity Institutions with social responses for the elderly in Northern *** enriches the literature by clarifying the concept of innovation applied to non-profit organizations,which represents a perspective different from the business ***,it is important to support the innovation decisionmaking process in similar non-profit *** this study,the population was surveyed through questionnaires based on the PUBLIN research project,which has already been applied in different countries,and the targets were employees of organizations with social responses for the *** sample is small,with 28 respondent institutions and 51 employees,but it is representative,as it includes institutions from all districts in Northern *** study employed a quantitative approach,particularly factor analysis,multiple linear regression,and correlation analyses,using scales already applied in other dimensions of the social sector,to understand the effect of each innovation dimension/determinant on creativity and innovation in nonprofit *** results show that in these organizations with social responses for the elderly,learning orientation,risk-taking,and job satisfaction have a positive impact on innovation.

关键词： Determinants of innovation non-profit organizations social responses for the elderly Northern Portugal

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab alexandra Kretz Computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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*** 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

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Sarcopenic obesity in patients awaiting liver transplant: Unique challenges for nutritional recommendations

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World Journal of Transplantation 2024年第2期14卷 40-47页

作者： Darya M Herscovici Katherine M Cooper Alessandro Colletta Michelle Rightmyer alexandra Shingina Lauren D Feld Department of Medicine UMass Chan Medical SchoolWorcesterMA 01655United States Division of Transplant Nutrition UMass Chan Medical SchoolWorcesterMA 01655United States Department of Medicine Vanderbilt University Medical CenterNashvilleTN 37215United States Division of Gastroenterology UMass Chan Medical SchoolWorcesterMA 01655United States

Sarcopenic obesity increases the risk of mortality in patients with liver disease awaiting liver transplantation and in the post-transplant *** recommendations for individuals with sarcopenia differ from recommendations for patients with obesity or sarcopenic *** these nutrition guidelines have been established in non-cirrhotic patients,established guidelines for liver transplant candidates with sarcopenic obesity are *** this paper,we review existing literature on sarcopenic obesity in patients with chronic liver disease and address opportunities to improve nutritional counseling in patients awaiting liver transplantation.

关键词： Nutrition Sarcopenia Sarcopenic obesity Liver transplant Cirrhosis Chronic liver disease Body composition Myostatin

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