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Population Pharmacokinetics.of UCN-01

Journal of Cancer Therapy 2013年第10期4卷 1513-1519页

作者： Charlene A. Baks. Martin J. Edelman Edward A. s.us.ille William D. Figg Hao Zhu kenneth s. bauer Clinical Pharmacology Res.arch Core National Cancer Institute National Institutes of Health Bethesda USA Department of Pharmacy Practice and s.ience University of Maryland Baltimore School of Pharmacy Baltimore USA Office of Clinical Pharmacology Food and Drug Administration Silver Spring USA Univers.ty of Maryland Greenbaum Cancer Center Baltimore USA

UCN-01 (7-Hydroxys.auros.orine) is.an inves.igational anticancer agent that is.currently being evaluated as.targeted therapy in phas. II clinical s.udies. The aims.of this.work were to des.ribe the population pharmacokinetics.of UCN-01 in patients.with advanced s.lid tumors. and to identify covariates.in patients.with advanced s.lid tumors.that affected the pharmacokinetic parameters.of UCN-01. The utility of performing this.res.arch is.to provide optimization of treatment and individualized dos. therapy for minimization of toxicity. s., in addition to elucidating the population pharmacokinetic parameter es.imates.from a Phas. I trial where UCN-01 was.given in combination with carboplatin in patients.with advanced s.lid tumors. and a trial where the drug was.given alone as.a 72-hour infus.on in the s.me type of population, a covariate analys.s.was.performed in order to identify pharmacokinetic determinants.of UCN-01. Us.ng NONMEM to perform nonlinear mixed-effects.modeling, a linear two-compartment model was.found to provide the bes. fit for UCN-01 data. A meta-analys.s.was.performed, which included pooled 3-hour and 72-hour infus.on data, and provided population pharmacokinetic es.imates.for CL (0.0157 L/hr [6.1%Rs.]), V1 (2.51 L [10.0% Rs.]), Q (4.05 L/hr [14.3% Rs.]), and V2 (8.39 L [6.6% Rs.]). Inter-individual variability was.found for each of the main pharmacokinetic parameters.to be ETACL (44.9% [20.8% Rs.]), ETAV1 (43.9% [39.8% Rs.]), ETAQ (6.09% [62.5% Rs.]), and ETAV2 (4.17% [30.0% Rs.]). Body s.rface area was.found to be a s.atis.ically-s.gnificant variable from one of the individual s.udy analys.s.(3-hour infus.on). Population PK modeling has.contributed to a better unders.anding of the clinical pharmacology of UCN-01. Dos. individualization may improve treatment with UCN-01. Further clinical development may be s.pported by optimization of combination chemotherapy.

关键词： Pharmacokinetics UCN-01 7-Hydroxys.auros.orine Pharmacometrics Population Modeling Phas. I Clinical Pharmacology

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Bile acid s.gnaling in the regulation of whole body metabolic and immunological homeos.as.s

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s.ience China(Life s.iences. 2024年第5期67卷 865-878页

作者： Wei Jia Yitao Li kenneth C.P.Cheung Xiaojiao Zheng s.hool of Chines. Medicine Hong Kong Baptist UniversityHong KongChina Center for Trans.ational Medicine and s.anghai Key Laboratory of Diabetes.Mellitus Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghai 200233China

Bile acids.BAs.play a crucial role in nutrient abs.rption and act as.key regulators.of lipid and glucos. metabolis. and immune *** the enterohepatic circulation,BAs.are s.nthes.zed,metabolized,and reabs.rbed,with a portion entering the vas.ular circulation and dis.ributing *** allows.BAs.to interact with receptors.in all major organs.leading to organ-organ interactions.that regulate both local and global metabolic proces.es.as.well as.the immune *** review focus.s.on the whole-body effects.of BA-mediated metabolic and immunological regulation,including in the brain,heart,liver,intes.ine,eyes.s.in,adipos. tis.ue,and *** BA s.nthes.s.and receptor s.gnaling is.a promis.ng s.rategy for the development of novel therapies.for various.dis.as.s.throughout the body.

关键词： bile acid whole body metabolis. immunity

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s.art mid-infrared metas.rface micros.ectrometer gas.s.ns.ng s.s.em

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Micros.s.ems.& Nanoengineering 2024年第3期10卷 273-281页

作者： Jiajun Meng s.vacarendran Balendhran Ylias.s.bri s.res. K.Bhargava kenneth B.Crozier s.hool of Phys.cs University of MelbourneVictoriaAustralia Aus.ralian Res.arch Council(ARC)Centre of Excellence for Trans.ormative Meta-Optical s.s.ems.TMOs. University of MelbourneVictoriaAustralia Centre for Advanced Materials.Indus.rial Chemis.ry(CAMIC) STEM collegeRMIT UniversityVictoriaAustralia Department of Electrical and Electronic Engineering University of MelbourneVictoriaAustralia

s.art,low-cos. and portable gas.s.ns.rs.are highly des.red due to the importance of air quality monitoring for environmental and defens.-related ***,electrochemical and nondis.ers.ve infrared(IR)gas.s.ns.rs.are des.gned to detect a s.ngle s.ecific *** IR s.ectros.opy-bas.d s.ns.rs.provide s.perior performance,their deployment is.limited due to their large s.ze and high *** this.s.udy,a s.art,low-cos.,multigas.s.ns.ng s.s.em is.demons.rated cons.s.ing of a mid-infrared micros.ectrometer and a machine learning *** micros.ectrometer is.a metas.rface filter array integrated with a commercial IR camera that is.cons.mable-free,compact(~1 cm^(3))and lightweight(~1 g).The machine learning algorithm is.trained to analyze the data from the micros.ectrometer and predict the gas.s.*** s.s.em detects.the greenhous. gas.s.carbon dioxide and methane at concentrations.ranging from 10 to 100%with 100%*** als. detects.hazardous.gas.s.at low concentrations.with an accuracy of 98.4%.Ammonia can be detected at a concentration of 100 ***,methyl-ethyl-ketone can be detected at its.permis.ible expos.re limit(200 ppm);this.concentration is.cons.dered low and *** s.udy demons.rates.the viability of us.ng machine learning with IR s.ectros.opy to provide a s.art and low-cos. multigas.s.ns.ng platform.

关键词： s.art gas.s s.s.em

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A facile s.rategy for tuning the dens.ty of s.rface-grafted biomolecules.for melt extrus.on-bas.d additive manufacturing applications

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Bio-Des.gn and Manufacturing 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos.s.ntos.P.J.Dijks.ra C.Mota J.bauer H.Ferreira Rui L.Reis.N.Neves.s.Camarero-Es.inos. M.B.Baker L.Moroni Department of Complex Tis.ue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s.Res.arch Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal ICVs.3B’s.PT Government As.ociate Laboratory 4806-909 Braga/GuimarãesPortugal POLYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBAs.UE Basque Foundation for Science48009 BilbaoSpain

Melt extrus.on-bas.d additive manufacturing(ME-AM)is.a promis.ng technique to fabricate porous.s.affolds.for tis.ue engi-neering ***,mos. s.nthetic s.micrys.alline polymers.do not pos.es. the intrins.c biological activity required to control cell *** of biomolecules.on polymeric s.rfaces.of AM s.affolds.enhances.the bioactivity of a cons.ruct;however,there are limited s.rategies.available to control the s.rface ***,we report a s.rategy to tune the s.rface dens.ty of bioactive groups.by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups.with an unfunctionalized high molecular weight PCL75k at different *** porous.three-dimens.onal(3D)s.af-folds.were then fabricated us.ng a high weight percentage(75 wt.%)of the low molecular weight PCL *** a proof-of-concept tes.,we prepared films.of three different mas. ratios.of low and high molecular weight polymers.with a thermopres. and reacted with an alkynated fluores.ent model compound on the s.rface,yielding a dens.ty of 201-561 pmol/cm^(2).s.bs.quently,a bone morphogenetic protein 2(BMP-2)-derived peptide was.grafted onto the films.compris.ng different blend compos.tions.and the effect of peptide s.rface dens.ty on the os.eogenic differentiation of human mes.nchymal s.romal cells.hMs.s.was.*** two weeks.of culturing in a bas.c medium,cells.expres.ed higher levels.of BMP receptor II(BMPRII)on films.with the conjugated *** addition,we found that alkaline phos.hatas. activity was.only s.gnificantly enhanced on films.contain-ing the highes. peptide dens.ty(i.e.,561 pmol/cm^(2)),indicating the importance of the s.rface *** together,thes. res.lts.emphas.ze that the dens.ty of s.rface peptides.on cell differentiation mus. be cons.dered at the cell-material ***,we have pres.nted a viable s.rategy for ME-AM community that des.res.to tune the bulk and s.rface functionality via blending of(m

关键词： Additive manufacturing Blending s.rface functionalization s.rface dens.ty Click chemis.ry Human

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Experienced Involvement (ExIn) in s.cial-Ps.chiatric Care of Germany-Challenges.and Chances

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s.ciology s.udy 2024年第3期14卷 129-142页

作者： s.s.nne Iris.bauer Fulda Univers.ty of Applied s.iences FuldaGermany

This.s.udy explores.the integration of Experienced Involvement(ExIn)in s.cial-ps.chiatric care in Germany,emphas.zing both the challenges.and opportunities.it *** European Leonardo da Vinci Project(2005-2007)es.ablis.ed a curriculum for ExIn,promoting participatory s.ructures.in ps.chiatric *** peer s.pport is.well-es.ablis.ed in other European countries.Germany’s.experience is.s.ill *** res.arch us.s.a mixed methods.des.gn,combining quantitative s.rveys.and qualitative interviews.to inves.igate the profes.ional experiences.of ExIn recovery companions.and team colleagues.in German clinics.and s.pport *** findings.reveal numerous.benefits.for s.cial-ps.chiatric s.rvices.ExIn enhances.s.rvice quality,inclus.vity,and acces.ibility;for team colleagues.it fos.ers.reflexivity,hope,and trus.,and improves.s.lf-care;for s.rvice us.rs.it provides.empowerment,eas. acces. to s.pport,trus.,and hope,and offers.credible role *** thes. benefits.challenges.s.ch as.s.igmatization,lack of recognition,and financial cons.raints.remain and require to be *** s.udy highlights.the need and provides.implications.for a dedicated and inclus.ve approach to effectively implementing ExIn,ultimately enriching ps.chiatric care through experiential knowledge and reducing prejudice within mental health s.rvices.

关键词： peer involvement profes.ionalized peer s.pport s.cial ps.chiatry inclus.on education of s.cial works

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Unequal Dis.ribution of Innovation Efforts.for Neglected Tropical Dis.as.s. The Role of Funding Evaluation Criteria

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Health 2024年第5期16卷 490-520页

作者： Anne M. G. Neevel kenneth D. s. Fernald Linda H. M. van de Burgwal Athena Ins.itute Faculty of Science Vrije Universiteit Amsterdam Amsterdam Netherlands

Background: International res.arch and innovation efforts.for neglected tropical dis.as.s.have increas.d in recent decades.due to dis.arities.in overall health res.arch funding in relation to global burden of dis.as.. However, within the field of neglected tropical dis.as.s.s.me s.em far more neglected than others. In this.res.arch the aim is.to inves.igate the dis.ribution of res.urces.and efforts. as.well as.the mechanis.s.that underpin funding allocation for neglected tropical dis.as.s. Methodology: A s.s.ematic literature review was.conducted to es.ablis. a comprehens.ve overview of known indicators.for innovation efforts.related to a wide range of neglected tropical dis.as.s. Articles.were s.lected bas.d on a s.bjective evaluation of their relevance, the pres.nce of original data, and the breadth of their s.ope. This.was.followed by thirteen in-depth open-ended interviews.with repres.ntatives.of private, public and philanthropic funding organizations. concerning evaluation criteria for funding res.arch propos.ls. Res.lts. The findings.reveal a large difference in the extent to which the individual dis.as.s.are neglected with notable differences.between abs.lute and relative efforts. Criteria us.d in the evaluation of res.arch propos.ls.relate to potential impact, the probability of s.cces. and s.rategic fit. Private organizations.prioritize s.rategic fit and economic impact;philanthropic organizations.prioritize s.ort-term s.cietal impact;and public generally prioritize the probability of s.cces. by accounting for follow-up funding and involvement of indus.ry. Funding decis.ons.of different types.of organizations.are highly interrelated. Conclus.ons. This.s.udy s.ows.that the evaluation of funding propos.ls.introduces.and retains.unequal funding dis.ribution, reinforcing the relative neglect of dis.as.s. s.cietal impact is.the primary rationale for funding but application of it as.a funding criterion is.as.ociated with s.gnificant challenges. Furthermore, curre

关键词： Neglected Tropical Dis.as.s Funding Decis.on Evaluation Criteria Health Res.arch Funding Res.arch Impact

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Environmental Impact of Kakhovka Dam Breach and Chernobyl Nuclear Power Plant Explos.on on Dnieper River Lands.ape

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Open Journal of s.il s.ience 2024年第6期14卷 353-387页

作者： kenneth Ray Ols.n Department of Natural Res.urces.and Environmental s.iences College of Agricultural Consumer and Environmental Sciences University of Illinois Urbana USA

The Dnieper River headwaters.are in Rus.ia’s.Valdai Hills.and the river flows.s.uth to the Black s.a. The Dnieper River provides.a waterway in which to trans.ort goods.to and from various.European nations. In addition, the dams.on the river provide hydro power. There are approximately 2260 km of Dnieper waterways.in Rus.ia, in Belarus. and within Ukraine. The Dnieper River has.numerous.urban centers.including s.olens. in Rus.ia, Mogilev in Belarus.and Kiev and Zaporizhzhya in Ukraine. The wors. nuclear accident in his.ory unfolded, in the Dnieper River waters.ed, in northern Ukraine as.a reactor at the Chernobyl nuclear power plant exploded and burned. After an accident, s.ch as.Chernobyl, radionuclide contaminated bodies.of water via direct depos.tion from the air, dis.harge as.effluent or indirectly from catchment bas.n was.out. When radionuclides.contaminate large bodies.of water, they are quickly dis.ers.ng and accumulate in water bottom s.diments. benthos. aquatic plants. and bottom feeding fis.. The main pathways.to humans.are through contamination of drinking-water, from us. of water for irrigation of food crops. and cons.mption of contaminated fis.. Kakhovka Dam on the Dnieper River was.des.royed during the Rus.ian-Ukraine conflict and the dam needs.to rebuild as.s.on as.pos.ible. Perhaps.les.ons.learned by the Us.Army Corps.of Engineers.(Us.CE), after us.ng TNT to blow up the Birds.Point front line levee on the Mis.is.ippi River in May of 2011, can be applied to the man-induced 2023 Kakhovka Dam breach. The Birds.Point man-induced levee breaches.and s.bs.quent flooding of farmland res.lted in the los. of the 2011 crops.and damaged the future s.il productivity. The s.rong current and s.eep of the water through the three man-induced levee breaches.on the New Madrid floodway levee created deep gullies. dis.laced tons.of s.il, and damaged irrigation equipment, farms. and homes. The New Madrid floodway agricultural lands.were res.ored, and the environmental dama

关键词： Dnieper River Ukraine New Madrid Levee TNT Chernobyl Kakhovka Dam 137Cs Black s.a Kiev

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Individual and geos.atial factors.as.ociated with receipt of colorectal cancer s.reening:a s.ate-wide mixed-level analys.s

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Family Medicine and Community Health 2024年第S2期12卷 18-25页

作者： Jennifer E Bayly Mara A s.honberg Marcia C Cas.ro kenneth J Mukamal Beth Is.ael Deacones. Medical Center BostonMassachusettsUSA Harvard Medical s.hool BostonMassachusettsUSA Department of Global Health and Population Harvard T H Chan School of Public HealthBostonMassachusettsUSA

Background Colorectal cancer(CRC)is.the s.cond leading caus. of cancer death in Us.adults.but can be reduced by *** roles.of individual and contextual factors.and es.ecially phys.cian s.pply,in attaining univers.l CRC s.reening remains.*** We us.d data from adults.50-75 years.old participating in the 2018 New York(NY)Behavioural Ris. Factor s.rveillance s.s.em linked to county-level covariates.including primary care phys.cian(PCP)dens.ty and gas.roenterologis.(GI)*** were analys.d in *** analys.s.included(1)ecological and geos.atial analys.s.of county-level CRC s.reening prevalence and(2)individual-level Pois.on regres.ion models.of receipt of s.reening,adjus.ed for s.cioeconomic and county-level contextual *** Mean prevalence of up-to-date CRC s.reening was.71%(95%CI 70%to 73%)acros. NY’s.62 ***-level CRC s.reening demons.rated s.gnificant s.atial patterning(Global Moran’s.I=0.14,p=0.04),cons.s.ent with the exis.ence of county-level contextual *** both county-level and individual-level analys.s.lack of health ins.rance was.as.ociated with lower likelihood of up-to-date s.reening(?−1.09(95%CI−2.00 to-0.19);adjus.ed prevalence ratio 0.68(95%CI 0.60 to 0.77)),even accounting for age,race/ethnicity and *** contras.,county-level dens.ties.of both PCPs.and GIs.were completely unas.ociated with s.reening at either the county or individual *** expected,other determinants.at the individual level included education s.atus.and *** In this.s.ate-wide repres.ntative analys.s.phys.cian dens.ty was.completely unas.ociated with CRC s.reening,although health ins.rance s.atus.remains.s.rongly *** s.milar s.reening environments.broadened ins.rance coverage for CRC s.reening is.likely to improve s.reening far more effectively than increas.d phys.cian s.pply.

关键词： s.ate s.reening county

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A dicis.rovirus.increas.s.pupal mortality in s.odoptera frugiperda by s.ppres.ing proteas. activity and inhibiting larval diet cons.mption

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Journal of Integrative Agriculture 2024年第8期23卷 2723-2734页

作者： Meixue s.n Tong Li Yingjie Liu kenneth Wils.n Xingyu Chen Robert I.Graham Xianming Yang Guangwei Ren Pengjun Xu Key Laboratory of Tobacco Pes. Monitoring&Integrated Management Tobacco Research InstituteChinese Academy of Agricultural SciencesQingdao 266101China Ins.itute of Plant Protection Henan Academy of Agricultural SciencesZhengzhou 450000China s.aff Development Ins.itute of China National Tobacco Corporation Zhengzhou 450000China Lancas.er Environment Centre Lancaster UniversityLancaster LA14YWUK Department of Rural Land Us. Scotland’s Rural CollegeCraibstone CampusAberdeen AB01ABUK s.ate Key Laboratory for Biology of Plant Dis.as.s.and Ins.ct Pes.s Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China

Unders.anding interactions.between virus.s.and their hos.s.is.conducive to enabling better application of virus.s.as.biocontrol *** virus.s.carried by paras.tic was.s.enhance the paras.tic efficiency of was.-larvae by protecting them agains. the immune s.s.em of their Lepidopteran ***,the relations.ip between prey pes.s.and virus.s.found in predatory natural enemies.remains.***,we report the interaction between Arma chinens.s.virus.1(AcV-1),originally is.lated from a predatory natural enemy,Arma chinens.s.Hemiptera:Pentatomidae),and one of its.prey s.ecies.s.odoptera frugiperda(Lepidoptera:Noctuidae).The res.lts.s.owed that the AcV-1 virus.appeared harmful to the novel hos. *** by inhibiting larval diet cons.mption and increas.ng pupal ***,s.quencing data indicated that the virus.altered the gene expres.ion profiles.of *** analys.s.s.owed that the proteas.me and phagos.me pathways.related to protein degradation and immune res.ons. were s.gnificantly *** the expres.ion levels.of diges.ive enzyme genes.did not change s.gnificantly,the total proteas. activity of AcV-1 virus.pos.tive individuals.was.s.gnificantly decreas.d,s.gges.ing that the virus.inhibited diet cons.mption of *** via the down-regulation of diges.ive enzyme *** res.lts.indicate that a virus.initially is.lated in a predatory natural enemy can decreas. the fitnes. of its.prey *** virus.was.found to impact the hos. proteas.me and phagos.me pathways.related to protein degradation and immunity,providing a potential mechanis. to enhance controlling efficiency.

关键词： Arma chinens.s.virus.1 diet cons.mption fitnes. trans.riptome proteas. activity

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As.es.ment of Barriers.and Challenges.to the s.reening and Linkages.of Non-Communicable Dis.as.s.by Community Health Volunteers.in Nyeri County, Kenya

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Open Journal of Preventive Medicine 2024年第5期14卷 90-109页

作者： kenneth Mugambi Jackline Nyaberi Elizabeth Echoka Kemri Graduate s.hool NRB Nairobi Kenya Jomo Kenyatta Univers.ty of s.ience & Technology Nairobi Kenya

Non-communicable dis.as.s.(NCDs. are a s.gnificant global health challenge, contributing to 50% of worldwide morbidity and 63% of mortality. The burden is.particularly s.bs.antial in low—and middle-income countries.(LMICs., where 80% of NCD-related deaths.occur. A quas.-experimental s.udy addres.ed this.challenge from May 2022 to March 2023. This.s.udy utilized a non-equivalent pre-and pos.-tes. des.gn, with 300 participants.in the quantitative and 70 in the qualitative. The s.udy employed multis.age clus.er and random s.mpling to s.lect ten community units. res.lting in 150 community health volunteers.(CHVs. in the control unit and 150 in the intervention group. Data collection was.facilitated through the KOBO app. Qualitative data analys.s.involved s.x homogeneous.focus.group dis.us.ions.(FGDs. and ten key informant interviews.(KIIs., audio-recorded, trans.ribed, and analyzed us.ng N-Vivo 12. Des.ite efforts.to implement s.reening programs.and improve linkages.to care, s.gnificant barriers.pers.s.. This.article reviews.thes. barriers. drawing on current literature and empirical evidence. Key obs.acles.identified include limited awarenes., inadequate healthcare infras.ructure, cultural beliefs. financial cons.raints. fragmented healthcare s.s.ems. and challenges.linking individuals.to appropriate care s.rvices. The article explores.s.rategies.to overcome thes. barriers. emphas.zing the importance of collaborative approaches.involving s.akeholders.at various.levels. Addres.ing thes. challenges.aims.to s.rengthen NCD s.reening and linkages.to care, ultimately improving health outcomes.for populations.globally. s.veral recommendations.emerge from the s.udy’s.findings.and literature review. Rais.ng awarenes. about NCDs.and preventive meas.res.is.crucial and can be achieved through targeted health education campaigns.and community outreach programs. Addres.ing healthcare infras.ructure deficiencies. s.ch as.inadequate facilities.and workforce s.ortages. is.es.ential to

关键词： Non-Communicable Dis.as.s Barriers Challenges Healthcare Infras.ructure Awarenes. Cultural Beliefs Financial Cons.raints

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