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RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce daniel martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established treatments.Growing evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment strategy.In this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical models.Histological analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL inhibition.RNA sequencing of human and mouse tissue supported these findings.The interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on osteoclasts.The results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within lesions.These findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

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Vonoprazan-amoxicillin dual regimen with Saccharomyces boulardii as a rescue therapy for Helicobacter pylori:Current perspectives and implications

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World Journal of Gastroenterology 2024年第10期30卷 1280-1286页

作者： Valerie Josephine Dirjayanto Jessica Audrey daniel martin Simadibrata Faculty of Medicine Universitas IndonesiaJakarta Pusat 10430DKI JakartaIndonesia Division of Gastroenterology and Hepatology Mayo ClinicRochesterMinnesota 55905United States Nuffield Department of Population Health University of OxfordOxford OX37LFUnited Kingdom

Yu et al’s study in the World Journal of Gastroenterology(2023)introduced a novel regimen of Vonoprazan-amoxicillin dual therapy combined with Saccharomyces boulardii(S.boulardii)for the rescue therapy against Helicobacter pylori(H.pylori),a pathogen responsible for peptic ulcers and gastric cancer.Vonoprazan is a potassium-competitive acid blocker renowned for its rapid and long-lasting acid suppression,which is minimally affected by mealtime.Compared to proton pump inhibitors,which bind irreversibly to cysteine residues in the H+/K+-ATPase pump,Vonoprazan competes with the K+ions,prevents the ions from binding to the pump and blocks acid secretion.Concerns with increasing antibiotic resistance,effects on the gut microbiota,patient compliance,and side effects have led to the advent of a dual regimen for H.pylori.Previous studies suggested that S.boulardii plays a role in stabilizing the gut barrier which improves H.pylori eradication rate.With an acceptable safety profile,the dual-adjunct regimen was effective regardless of prior treatment failure and antibiotic resistance profile,thereby strengthening the applicability in clinical settings.Nonetheless,S.boulardii comes in various formulations and dosages,warranting further exploration into the optimal dosage for supplementation in rescue therapy.Additionally,larger,randomized,double-blinded controlled trials are warranted to confirm these promising results.

关键词： Vonoprazan Saccharomyces boulardii Helicobacter pylori Rescue therapy Eradication rate

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新天鹅护理休闲区,本特利,澳大利亚

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世界建筑 2024年第6期 66-71页

作者：无 Adrian Iredale Finn Pedersen Martyn Hook Tom See Hoo Rebecca Angus Mary McAree Rebecca Hawkett Catherine Dupuy Gian Tonossi Jordan Blagaich Jake Gethin daniel martin Peter Bennetts(摄影) 伊代尔-佩德森-霍克建筑事务所不详

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林... 详细信息

新天鹅护理休闲区旨在通过减少隔离、鼓励安全的活动和社交互动来改善居民的健康和福祉,并欢迎朋友、家人和周边居民的到来。Iph建筑事务所挑战了之前的总体规划,将车辆和道路从中心空间移除,取而代之的是一条宽阔、笔直且清静的人行林荫道。林荫大道从天鹅护理中心的主要入口街道(阿迪苑)延伸至新的休闲区,并继续通向到远处的老年人关怀设施。一条蜿蜒曲折的小路与林荫大道相接,方便人们慢步闲逛。随着总体规划逐渐深化,这些小路将继续延伸,为老年痴呆症患者提供安全的活动空间。

关键词：护理中心建筑事务所主要入口林荫大道本特利休闲区蜿蜒曲折林荫道

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Impact of postoperative intravenous fluid administration on complications following elective hepato-pancreato-biliary surgery

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 402-407页

作者： daniel martin Panagis M.Lykoudis Gabriel Jones David Highton Alan Shaw Sarah James Qiang Wei Giuseppe Fusai Division of Surgery&Interventional Science University College LondonGower StBloomsburyLondonWC1E 6BTUK Free Perioperative Research Group Royal Free HospitalPond stLondonNW3 2QGUK Department of Hepato-Pancreato-Biliary Surgery&Liver Transplantation Royal Free HospitalPond stLondonNW3 2QGUK King’s College Hospital Denmark HillLondon SE5 9RSUK Neurocritical Care Unit the National Hospital for Neurology and NeurosurgeryQueen SquareLondonWC1N 3BGUK London School of Hygiene&Tropical Medicine Keppel StreetLondonWC1E 7HTUK Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryFirst Affiliated HospitalZhejiang University School of Medicine79 Qingchun RoadHangzhou 310003China

Background: The impact of perioperative intravenous fluid administration on surgical outcomes has been documented in literature, but not specifically studied in the context of hepato-pancreato-biliary(HPB) surgery. This study aimed to investigate the impact of postoperative intravenous fluid administration on intensive care unit(ICU), in this subgroup of patients. Methods: A single-center retrospective cohort of 241 HPB patients was assessed, focusing on intravenous fluid administration in ICU, during the first 24 h. Intravenous fluid variables were compared to hospital stay and postoperative complications. Data were assessed using Spearman's correlation test for bivariate correlations and logistic regression for multivariate analysis. Results: The median volume of intravenous fluid administered in the first 24 h postoperatively was 4380 mL, of which 2200 mL was crystalloid, 1500 mL colloid and 680 mL "other" fluid. Patients with one or more complications had a higher median total intravenous fluid input(4790 vs. 4300 mL), higher colloid volume(20 0 0 vs. 150 0 mL), lower urine output(1595 vs. 1900 mL) and greater overall fluid balance( + 3040 vs. + 2553 mL) than those without complications. There were correlations between total intravenous fluid volume administered( r = 0.278, P < 0.001), intravenous colloid input( r = 0.278, P < 0.001), urine output( r =-0.295, P < 0.001), positive fluid balance( r = 0.344, P < 0.001) and length of hospital stay. Logistic regression model was constructed to predict the occurrence of one or more complications; total intravenous fluid volume and overall fluid balance were both independent significant predictors(OR = 2.463, P = 0.007; OR = 1.001, P = 0.011; respectively). Conclusions: Administration of high volumes of intravenous fluids in the first 24 hours post-HPB surgery, along with higher positive fluid balance is associated with a higher rate of complications and longer hospital stay. Moreover, lower urine output is associated with longer hospital stay. Whether these are the

关键词： Intravenous fluids Hepato-pancreato-biliary surgery Postoperative outcome

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Left lateral decubitus sleeping position is associated with improved gastroesophageal reflux disease symptoms: A systematic review and meta-analysis

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World Journal of Clinical Cases 2023年第30期11卷 7329-7336页

作者： daniel martin Simadibrata Elvira Lesmana Bagus Ramasha Amangku Muhammad Prasetio Wardoyo Marcellus Simadibrata Department of Internal Medicine Faculty of Medicine Universitas IndonesiaJakarta 10430Indonesia Nuffield Department of Population Health University of OxfordOxford OX37LFUnited Kingdom Division of Gastroenterology and Hepatology Mayo ClinicRochesterMN 55905United States Division of Gastroenterology Department of Internal MedicineFaculty of Medicine Universitas IndonesiaJakarta 10430Indonesia

BACKGROUND A limited number of studies have demonstrated that sleeping in the left lateral decubitus(LLD)decreases nocturnal reflux in patients with gastroesophageal reflux disease(GERD)compared to right lateral decubitus(RLD)and supine.AIM This systematic review summarizes the association between sleeping in the LLD position and nocturnal reflux in patients with GERD.METHODS Studies published up to July 17,2023,in MEDLINE,EMBASE,and CENTRAL were searched.Eligible studies were randomized and nonrandomized studies assessing the effect of sleeping in LLD compared to RLD and supine in reducing nocturnal reflux in GERD patients.Outcomes include the acid exposure time(AET)(%time in pH<4),acid clearance time(ACT)(in sec/episode),number of reflux episodes,and improvement in N-GSSIQ scores.RESULTS Two nonrandomized studies showed decreased AET and ACT in LLD sleep position in comparison to RLD(mean difference[MD]-2.03[95%CI:-3.62 to-0.45];-81.84[95%CI:-127.48 to-36.20],respectively)and supine position(MD-2.71[95%CI:-4.34 to-1.09];-74.47[95%CI:-116.26 to-32.69],respectively).There was no difference in AET and ACT between RLD sleep position and supine.Furthermore,one randomized controlled trial investigating the use of electronic sleep positional therapy,which increased the duration of LLD sleep and decreased the duration of RLD sleep compared to sham,showed nocturnal symptoms improvement(improved N-GSSIQ score,increased reflux-free nights,and resolution of nocturnal reflux symptoms).CONCLUSION Current evidence suggests that sleeping on the left side could reduce nocturnal reflux and improve GERD-related quality of life,therefore warranting interventions that promote LLD sleep position.

关键词： Gastroesophageal reflux disease Left lateral decubitus Sleep position Systematic review

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Recent advances in vaccination of non-responders to standard dose hepatitis B virus vaccine

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World Journal of Hepatology 2015年第24期7卷 2503-2509页

作者： Saqib Walayat Zohair Ahmed daniel martin Srinivas Puli Michael Cashman Sonu Dhillon Department of Gastroenterology andHepatology University of Illinois PeoriaCampusOSF Saint Francis Medical Center Department of Internal Medicine Universityof Illinois Peoria CampusOSF Saint Francis Medical Center

Hepatitis B virus(HBV) infection is a global health problem. It is estimated there are more than 2 billion individuals exposed to the virus and 250 million are chronically infected. Hepatitis B is the cause of more than 600000 annual deaths due to cirrhosis and hepatocellular carcinoma. An effective vaccine exists and preventative initiatives center around universal vaccination especially in those at highest risk. Effective vaccination algorithms have led to a significant decline in the development of new infections and its devastating consequences. The vaccine is administered intramuscularly in three doses, with 95% showing long lasting serologic immunity. An additional fourth dose or a repeated higher dose three course regimen is given to those that fail to show immunity. Despite these additional regimens, some remain vulnerable to hepatitis B and are deemed nonresponders. Individuals with chronic disease states such as kidney disease, liver disease, diabetes mellitus, as well as those with a genetic predisposition, and those on immunomodulation therapy, have the highest likelihood of non-response. Various strategies have been developed to elicit an immune response in these individuals. These include increased vaccination dose, intradermal administration, alternative adjuvants, alternative routes of administration, co-administration with other vaccines, and other novel therapies. These alternative strategies can show improved response and lasting immunity. In summary, HBV vaccination is a major advance of modern medicine and all individuals at risk should be sought and vaccinated with subsequent adequate titers demonstrated.

关键词： Hepatitis B vaccine Non-responders Intradermal vac

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A Comparative Study of Non-Volatile Compounds Present in 3R4F Cigarettes and iQOS Heatsticks Utilizing GC-MS

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American Journal of Analytical Chemistry 2019年第3期10卷 76-85页

作者： Miguel Penin Ibanez daniel martin Alicia Gonzalez Gonzalvez Helmut H.Telle Angel Gonzalez Urena Departamento de Quimica Fisica Aplicada Facultad de CienciasUniversidad Autonoma de MadridMadridSpain

It is now widely suggested that people who are dependent on nicotine should switch from ordinary tobacco smoking to alternative products, which at least reduce the overall harm from smoking. A number of alternatives are now popular, including electronic cigarettes and heatsticks. In this work comparative analysis of the smoke/aerosol emission from 3R4F standard cigarettes and iQOS heatsticks was undertaken. For this, gas chromatography-mass spectrometry (GC-MS) analysis was applied, to measure the non-volatile compounds of smoke/aerosol emission from individual samples, with the specific aim to determine their content of nicotine and selected other main components. All measurement data were collected under the Health Canada Intense (HCI) puffing regime. The most relevant findings of the present investigation can be summarized as follows. First, the number of measured aerosol components in the iQOS samples, with respect to those of 3R4F samples, was significantly lower (notably 37 versus 12 components). Second, the analysis of the iQOS and 3R4F GC-MS chromatographic fingerprints indicated a non-nicotine global component reduction (number and areas excluding nicotine) of larger than 80% for the iQOS samples in comparison to 3R4F samples. Third, the nicotine content of the iQOS aerosol was less than half that contained in the 3R4F smoke. The results from the present investigation indicate that—except for nicotine—smokers are exposed to a largely reduced number and amount of non-volatile, non-nicotine components in the iQOS heatstick aerosol, in comparison to those in the 3R4F cigarette smoke.

关键词： Cigarette Heatstick Chromatographic Analysis Nicotine Tobacco Harm Reduction(THR)

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Predicting intensive care unit-acquired weakness:A multilayer perceptron neural network approach

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World Journal of Clinical Cases 2024年第12期12卷 2023-2030页

作者： Carlos martin Ardila daniel González-Arroyave Mateo Zuluaga-Gómez Department of Basic Sciences University of AntioquiaMedellín 52-59Colombia Department of Surgery Pontificia Universidad BolivarianaMedellín 0057Colombia Department of Emergency Universidad Pontificia BolivarianaMedellín 0057Colombia

In this editorial,we comment on the article by Wang and Long,published in a recent issue of the World Journal of Clinical Cases.The article addresses the challenge of predicting intensive care unit-acquired weakness(ICUAW),a neuromuscular disorder affecting critically ill patients,by employing a novel processing strategy based on repeated machine learning.The editorial presents a dataset comprising clinical,demographic,and laboratory variables from intensive care unit(ICU)patients and employs a multilayer perceptron neural network model to predict ICUAW.The authors also performed a feature importance analysis to identify the most relevant risk factors for ICUAW.This editorial contributes to the growing body of literature on predictive modeling in critical care,offering insights into the potential of machine learning approaches to improve patient outcomes and guide clinical decision-making in the ICU setting.

关键词： Intensive care units Intensive care unit-acquired weakness Risk factors Machine learning Computer neural network

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Alcohol and illicit drugs:prevalence of alcohol and illicit drug use and their predictors in young people from Argentina,Bulgaria,Chile and Romania

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Global Health Journal 2024年第1期8卷 16-23页

作者： daniel Vankov David Jankovszky Borislav Vankov martin Galanternik Claudia Rodriguez Michiel de Ruyter Scientific Organization from Partium Oradea 410204Romania Queensland University of Technology BrisbaneQueensland 4001Australia Association for Youth and Students in Partium Oradea 410102Romania Community Centre Bright Day-2009 Vidin 3700Bulgaria MiNU Civil.Association Buenos Aires 4918Argentina ONG No Chat Santiago 832000Chile

Background:Alcohol and illicit drugs(AID)continue to be a major global health concern.Although preventable,AID is linked to millions of deaths annually worldwide.The situation is particularly grave for young people,with AID being a major direct risk factor for disability-adjusted youth life-years lost and death.It further contributes to assaults,road crashes,accidental poisoning,and suicide,leading to long-term issues and public health concerns.Objective:This study aimed at disclosing current AID prevalence data for Argentinian,Bulgarian,Chilean and Romanian youth.It shed light on the predictors of AID in young people from those countries.Method:The study used an online survey to gather data from people aged 18 to 25(n=1,297).The survey was underpinned by the theory of planned behaviour(TPB).Predictors were investigated separately for drinking alcohol and using illicit drugs.Results:Our data revealed that across the four target countries,49%to 90%of the participants drank alcohol,and 8%to 35%used illicit drugs in the past three months.Between 20%and 91%of them intended to drink,and between 8%and 31%intended to use illicit drugs in the following three months.Our TPB model predicted statistically significant(P<0.001)amounts of variance in drinking alcohol(between 61%and 72%)and using illicit drugs(between 20.3%and 74.4%).Intention was consistent in significantly predicting both behaviours.Evidence around the predictive validity of self-efficacy,age and gender was mixed across the investigated countries.Conclusion:This research provided an update on the scarce AID epidemiological data.It also supplied evidence about what theoretically-informed measures might be useful targets of interventions in the case of Argentina,Bulgaria,Chile and Romania.This new knowledge of understanding substance abuse determinants and prevalence may help researchers and practitioners better meet young people's health prevention needs.

关键词： Young people Alcohol Ilicit drugs Intention Self-efficacy

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A Trip to China

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Voice of Friendship 2013年第4期 48-48页

作者： daniel martin

Editor’s Note:The Vermont School of Colombia is one of the few middle schools in the country that teaches Chinese as the second foreign language.In early June 2013,a 77-member student delegation came to China to attend a summer camp jointly hosted by the Chinese People’s Association for Friendship with Foreign Countries(CPAFFC)and the North China University of Technology(NCUT).The following is an essay written in Chinese by a Colombian student recording his tour in China.

关键词： delegation jointly recording schools essay attend

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