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Clinical studies in COVID-related olfactory disorders:Review of an institutional experience

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 129-136页

作者： Theresa Tharakan Dorina Kallogjeri Jay F.Piccirillo Department of Otolaryngology-Head and Neck Surgery Clinical Outcomes Research OfficeSchool of MedicineWashington University in St LouisSt LouisMissouriUSA

Objective:To share a single institutional experience with clinical research on COVID-related olfactory dysfunction(OD).Data Source/Method:Narrative review of published original data and ongoing clinical trials on COVID-related OD at Washington University from 2020 to ***:There were three new diagnostic-/patient-reported outcome measures developed and *** report five clinical trials of interventions for COVID-related olfactory disorders:combined Visual-Olfactory Training(VOLT)with patient-preferred scents versus standard olfactory training(VOLT trial),oral gabapentin versus placebo(Gabapentin for the Relief of Acquired Chemosensory Experience trial),nasal theophylline irrigations versus placebo(Smell Changes and Efficacy of Nasal Theophylline trial),stellate ganglion block(single-arm),and mindfulness-based stress reduction(MBSR)versus lifestyle intervention(MBSR trial).Conclusions:Initial intervention trials for COVID-related OD have shown potential for improving subjective and objective olfactory ***,there remains no gold standard treatment that definitively outperforms placebo in controlled ***,continued investigation of novel therapeutic strategies for COVID-related OD is necessary to maximize olfactory outcomes for affected patients.

关键词： chemosensory disorders COVID olfactory dysfunction

Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice:One-year observational study

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World Journal of Diabetes 2024年第3期15卷 455-462页

作者： Ahmed Eldib Shilton Dhaver Karim Kibaa Astrid Atakov-Castillo Tareq Salah Marwa Al-Badri Abdelrahman Khater Ryan McCarragher Omnia Elenani Elena Toschi Osama Hamdy Department of Clinical Behavioral&Outcomes ResearchJoslin Diabetes CenterBostonMA 02215United States Department of Medicine Harvard Medical SchoolBostonMA 02115United States

BACKGROUND In 2016,the Food and Drug Administration approved the first hybrid closed-loop(HCL)insulin delivery system for adults with type 1 diabetes(T1D).There is limited information on the impact of using HCL systems on patient-reported outcomes(PROs)in patients with T1D in real-world clinical *** this independent study,we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic’s 670G HCL in real-world clinical *** To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with *** We evaluated 71 patients with T1D(mean age:45.5±12.1 years;59%females;body weight:83.8±18.7 kg,body mass index:28.7±5.6 kg/m2,A1C:7.6%±0.8%)who were treated with HCL at Joslin Clinic from 2017 to *** measured A1C and percent of glucose time-in-range(%TIR)at baseline and 12 *** measured percent time in auto mode(%TiAM)for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes *** At 12 mo,A1C decreased by 0.3%±0.1%(P=0.001)and%TIR increased by 8.1%±2.5%(P=0.002).The average%TiAM was only 64.3%±32.8%and was not associated with A1C,%TIR or ***,provided at baseline and at the end of the study,showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9%(P<0.001).Hypoglycemia fear survey/worry scale decreased significantly by 24.9%(P<0.000);Problem Areas In Diabetes reduced significantly by-17.2%(P=0.002).The emotional burden submodules of dietary diversity score reduced significantly by-44.7%(P=0.001).Furthermore,analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic ***-5 showed no improvements in subject’s wellbeing among participants after starting the 670G HCL ***,analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality,sleep latency,or duration o

关键词： Artificial pancreas Continuous blood glucose monitor Type 1 diabetes Hybrid closed-loop insulin delivery Quality of life

Tau in the pancreas:understanding the link between type 2 diabetes mellitus and Alzheimer's disease

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Signal Transduction and Targeted Therapy 2024年第1期9卷 6-7页

作者： Wenlu Li Steffen Tiedt Eng H.Lo Neuroprotection research Laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA02129USA consortium International pour la Recherche Circadienne sur l’AVC(CIRCA) BostonUSA Institute for Stroke and Dementia research LMU University HospitalLMU MunichMunichGermany

A recent study published in Molecular Psychiatry proposes a cellular mechanism that may contribute to decreased insulin production in individuals with type 2 diabetes mellitus(T2DM).1 Using a combination of cell culture experiments,animal models and studies in T2DM patients,the authors show that an up-regulation of tau inβ-islet cells can inhibit pancreatic insulin secretion through changes in microtubule assembly.

关键词： T2DM Alzheimer tau

AP4 induces JNK1 and a miR-22-3p/FOSL1 feed-forward loop to activate AP-1 and promote colorectal cancer metastasis

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Cancer Communications 2024年第3期44卷 433-437页

作者： Jinjiang Chou Markus Kaller Matjaz Rokavec Fangteng Liu Heiko Hermeking Experimental and Molecular Pathology Institute of PathologyMedical FacultyLudwig-Maximilians-Universität MünchenMunichGermany German Cancer consortium(DKTK) Partner siteMunichGermany German Cancer research Center(DKFZ) HeidelbergGermany

Dear Editor,Colorectal cancer(CRC)is the third most deadly can-cer worldwide[1].The mortality of CRC has remained high due to limited treatment options for metastatic CRC(mCRC)[2].Epithelial-mesenchymal transition(EMT)is an important contributor to mCRC[2].The c-MYC proto-oncogene(MYC)-induced transcription factor AP4(TFAP4/AP4)isadriverofEMT,therebypresumablyfacil-itates mCRC[3,4].The mitogen-activated protein kinase(MAPK)/c-JunN-terminalkinase(JNK)/activatorprotein-1(AP-1)pathway has been implicated in the regulation of EMT and mCRC[5].

关键词： JNK1 metastasis EMT

Harnessing naturally occurring mutations for T-cell therapy:a potential new avenue to enhance treatment efficacy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1799-1801页

作者： Michael Hiltensperger Jürgen Ruland Kilian Schober Mikrobiologisches Institut-Klinische Mikrobiologie Immunologie und HygieneFriedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany Institute of Clinical Chemistry and Pathobiochemistry School of MedicineTechnical University of MunichMunichGermany TranslaTUM Center for Translational Cancer ResearchTechnical University of MunichMunichGermany German Cancer consortium(DKTK) HeidelbergGermany German Center for Infection research(DZIF) partner site MunichMunichGermany FAU Profile Center Immunomedicine Friedrich-Alexander-Universität Erlangen-NürnbergErlangenGermany

In a recent study published in Nature,Garcia et *** a sophisticated approach to identify fitness-enhancing mutations for T cells that was inspired by cancer evolution.1 The identified CARD11-PIK3R3 gene fusion enhanced tumor rejection and persistence of engineered T cells in multiple tumor models and might have the potential to improve efficacy of adoptive T-cell therapies in cancer patients.

关键词： cancer potential

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

Synthesis of boron nitride nanorod and its performance as a metalfree catalyst for oxidative desulfurization of diesel fuel

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Chinese Journal of Chemical Engineering 2024年第4期68卷 120-132页

作者： Tanaz Ghanadi Gholamreza Moradi Alimorad Rashidi Catalyst research Center Faculty of Chemical and Petroleum EngineeringRazi UniversityKermanshahIran Nanotechnology research Center Research Institute of Petroleum Industry(RIPI)TehranIran

In order to reduce the sulfur compounds in diesel fuel,boron nitride(BN)has been used as a novel metal-free catalyst in the present *** nanocatalyst was synthesized via template-free approach followed by heating treatment at 900℃ in nitrogen atmosphere that the characteristics of the sample were identified by the X-ray diffraction,Fourier-transform infrared spectroscopy,Raman spectroscopy,field emission scanning electron microscopy,transmission electron microscopy,atomic force microscopy,and N2 adsorption-desorption *** results of structural and morphological analysis represented that BN has been successfully *** efficacy of the main operating parameters on the process was studied by using response surface methodology based on the Box-Behnken design *** prepared catalyst showed high efficiency in oxidative desulfurization of diesel fuel with initial sulfur content of 8040 mg·kg^(-1)*** statistical analysis,a significant quadratic model was obtained to predict the sulfur removal as a function of efficient *** maximum efficiency of 72.4%was achieved under optimized conditions at oxidant/sulfur molar ratio of 10.2,temperature of 71℃,reaction time of 113 min,and catalyst dosage of 0.36 ***,the reusability of the BN was studied,and the result showed little reduction in activity of the catalyst after 10 times ***,a plausible mechanism was proposed for oxidation of sulfur compounds on the surface of the *** present study shows that BN materials can be selected as promising metal-free catalysts for desulfurization process.

关键词： Desulfurization Boron nitride(BN)nanostructure Experimental design BoxeBehnken

Microstructure and properties of coarse-grained WC-10Co cemented carbides with different carbon contents during heat treatments

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Rare Metals 2024年第4期43卷 1786-1792页

作者： Yuan-Feng Xie Xing-Cheng Xie Zhong-Wu Li Rui-Jun Cao Zhong-Kun Lin Qing Li Chen-Guang Lin Powder Metallurgy and Special Materials research Department General Research Institute for Nonferrous MetalsBeijing100088China

The effects of cryogenic treatment(CT)and tempering-cryogenic treatment(TCT)on the microstructure and properties of coarse-grained WC-10Co cemented carbides with different carbon contents were *** binder phase,WC mean grain sizes,W solubility in the binder,relative magnetic s aturation,densities,hardness,wear resistance and second phase precipitation of cemented carbides with different heat treatments were *** results show that there are significant changes of microstructure and properties in the samples with CT and TCT,especially due to the precipitation of metastable nanoparticles W_(x)Co_(y)C_(z) in the binder during the heat treatments of CT and *** the simultaneous combination of microstructure and nanoparticle-reinforced binder,a dramatically improved combination of hardness and wear resistance of the samples after TCT has been achieved.

关键词： Cryogenic treatment Tempering Coarsegrained cemented carbide Carbon content Nanoparticlereinforced binder

Rodent management in Aotearoa New Zealand: approaches and challenges to landscape-scale control

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Integrative Zoology 2024年第1期19卷 8-26页

作者： John G.INNES Grant NORBURY Araceli SAMANIEGO Susan WALKER Deborah J.WILSON Manaaki Whenua-Landcare research HamiltonNew Zealand Manaaki Whenua-Landcare research AlexandraNew Zealand Manaaki Whenua-Landcare research AucklandNew Zealand Manaaki Whenua-Landcare research DunedinNew Zealand

Aotearoa—New Zealand has only four rodent species,all *** order of arrival,they are Pacific rat Rattus exulans,brown rat ***,house mouse Mus musculus,and black rat *** management in New Zealand aims mainly to conserve indigenous biodiversity rather than to protect crops or manage diseases,as is usual *** describe four major“regimes”and one major vision for rodent control in New Zealand to meet ecological restoration *** challenges for island eradications are for large islands that are remote or populated by *** 1080 is the only large-scale(tens of thousands of hectares)option for black rat control,but its application requires adjustment to counter subsequent rapid black rat ***“ecosanctuaries”(mean 720 ha)use ground-based traps and poisons to target mainly black rats and face constant *** with mammal-resistant fences(up to 3500 ha)limit reinvasion and target more pest species and have enabled the return of previously extirpated taxa to the main *** Free 2050 aims to eradicate the rat species(but not mice)plus some other introduced mammals from New Zealand by *** vision is not attainable with current tools,but research and experimental management is exploring techniques and *** large scale(to 100000 ha)at which black rats are now targeted for control to extremely low abundance seems to be unique to New Zealand.

关键词： black rat brown rat eradication house mouse rodent control