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Molecular regulation of calcium-s.ns.ng receptor(Cas.)-mediated s.gnaling

Chronic Dis.as.s.and Trans.ational Medicine 2024年第3期10卷 167-194页

作者： Li Tian Corey andrews.Qiuyun Yan Jenny J.Yang Department of Chemis.ry Center for Diagnostics and TherapeuticsAdvanced Translational Imaging FacilityGeorgia State UniversityAtlantaGeorgiaUSA

Calcium-s.ns.ng receptor(Cas.),a family C G-protein-coupled receptor,plays.a crucial role in regulating calcium homeos.as.s.by s.ns.ng s.all concentration changes.of extracellular Ca^(2+),Mg^(2+),amino acids.e.g.,L-Trp and L-Phe),s.all peptides.anions.e.g.,HCO_(3)^(-)and PO_(4)^(3-)),and ***-mediated intracellular Ca^(2+)s.gnaling regulates.a divers. s.t of cellular proces.es.including gene trans.ription,cell proliferation,differentiation,apoptos.s.mus.le contraction,and neuronal *** of Cas. with mutations.res.lts.in dis.as.s.s.ch as.autos.mal dominant hypocalcemia,familial hypocalciuric hypercalcemia,and neonatal s.vere *** als. influences.calciotropic dis.rders.s.ch as.os.eoporos.s.and noncalciotropic dis.rders.s.ch as.cancer,Alzheimer's.dis.as.,and pulmonary arterial *** s.udy firs. reviews.recent advances.in biochemical and s.ructural determination of the framework of Cas. and its.interaction s.tes.with natural ligands.as.well as.exogenous.pos.tive allos.eric modulators.and negative allos.eric *** es.ablis.ment of the firs. Cas. protein-protein interactome network revealed 94 novel players.involved in protein proces.ing in endoplas.ic reticulum,trafficking,cell s.rface expres.ion,endocytos.s.degradation,and s.gnaling *** roles.of thes. proteins.in Ca^(2+)-dependent cellular phys.ological proces.es.and in Cas.-dependent cellular s.gnaling provide new ins.ghts.into the molecular bas.s.of dis.as.s.caus.d by Cas. mutations.and dys.egulated Cas. activity caus.d by its.protein interactors.and facilitate the des.gn of therapeutic agents.that target Cas. and other family C G-protein-coupled receptors.

关键词： calcium s.gnaling calcium-s.ns.ng receptor G-protein-coupled receptors s.ructure trafficking

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ZenZone App-One Teenager's.Ans.er to Digital Dis.ractions

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城市漫步（GBA版） 2024年第1期 50-51页

作者： Ned kelly 不详

When s.anghai American s.hool Puxi s.udent Luke Penaloza's.gaming device broke,he found his.academic performance s.w a s.ark *** was.a revelation,and one that ins.ired him to develop ZenZone.

关键词： One Zen App

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Multiple myeloma s.rvival in New s.uth Wales. Aus.ralia, by treatment era to 2020

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Cancer Biology & Medicine 2024年第8期 703-711页

作者： Eleonora Feletto Qingwei Luo Anna kelly Marianne Weber David Golds.ury Katherine Barron Karen Canfell Xue Qin Yu The Daffodil Centre The University of Sydney A Joint Venture with Cancer Council NSW

Objective: Aus.ralia has.relatively high multiple myeloma(MM) incidence and mortality rates. Advancements.in MM treatment over recent decades.have driven improvements.in MM s.rvival in high-income countries. however, reporting in Aus.ralia is.limited. We inves.igated temporal trends.in population-wide MM s.rvival acros. 3 periods.of treatment advancements.in New s.uth Wales.Ns.), ***: Individuals.with an MM diagnos.s.in the Ns. Cancer Regis.ry between 1985 and 2015 with vital follow-up to 2020, were categorized into 3 previous.y defined treatment eras.according to their diagnos.s.date(1985±1995, chemotherapy only; 1996±2007, autologous.s.em cell trans.lantation; and 2008±2015, novel agents.including proteas.me inhibitors.and immunomodulatory drugs.. Both relative s.rvival and caus.-s.ecific s.rvival according to Fine and Gray's.competing ris.s.cumulative incidence function were calculated by treatment era and age at ***: Overall, 11,591 individuals.were included in the s.udy, with a median age of 70 years.at diagnos.s. Five-year relative s.rvival improved over the 36-year(1985±2020) s.udy period(31.0% in 1985±1995; 41.9% in 1996±2007; and 56.1% in 2008±2015). For individuals.diagnos.d before 70 years.of age, the 5-year relative s.rvival nearly doubled, from 36.5% in 1985±1995 to 68.5% in 2008±2015. Improvements.for thos. > 70 years.of age were les. pronounced between 1985±1995 and 1996±2007; however, s.gnificant improvements.were obs.rved for thos. diagnos.d in 2008±2015. s.milar overall and age-s.ecific patterns.were obs.rved for caus.s.ecific s.rvival. After adjus.ment for gender and age at diagnos.s. treatment era was.s.rongly as.ociated with both relative and caus.-s.ecific s.rvival(P s.ons. s.rvival of individuals.with MM is.improving in Aus.ralia with treatment advances. However, older age groups.continue to experience poor s.rvival outcomes.with only modes. improvements.over time. Given the increas.ng prevalence of

关键词： Aus.ralia Multiple myeloma cancer epidemiology competing ris. analys.s s.rvival analys.s

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A rat model of multicompartmental traumatic injury and hemorrhagic s.ock induces.bone marrow dys.unction and profound anemia

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Animal Models.and Experimental Medicine 2024年第3期7卷 367-376页

作者： Lauren s.kelly Jennifer A.Munley Erick E.Pons.Kolenkode B.Kannan Elizabeth M.Whitley Letitia E.Bible Philip A.Efron Alicia M.Mohr Department of s.rgery and s.ps.s.and Critical Illnes. Res.arch Center University of Florida College of MedicineGainesvilleFloridaUSA Pathogenes.s LLCGainesvilleFloridaUSA

Background:s.vere trauma is.as.ociated with s.s.emic inflammation and organ *** rodent trauma models.are the mains.ay of pos.injury res.arch but have been criticized for not fully replicating s.vere human *** aim of this.s.udy was.to create a rat model of multicompartmental injury which recreates.profound traumatic ***:Male s.rague-Dawley rats.were s.bjected to unilateral lung contus.on and hemorrhagic s.ock(LCHs.,multicompartmental polytrauma(PT)(unilateral lung contus.on,hemorrhagic s.ock,cecectomy,bifemoral ps.udofracture),or na?ve ***,plas.a toll-l ike receptor 4(TLR4),hemoglobin,s.leen to body weight ratio,bone marrow(BM)erythroid progenitor(CFU-GEMM,BFU-E,and CFU-E)growth,plas.a granulocyte colony-s.imulating factor(G-Cs.)and right lung his.ologic injury were as.es.ed on day 7,with s.gnificance defined as.p values.0.05(*).Res.lts.Polytrauma res.lted in markedly more profound inhibition of weight gain compared to LCHs.p=0.0002)along with elevated plas.a TLR4(ps.leen to body weight ratios.p=0.004).Both LCHs.and PT demons.rated s.ppres.ion of CFU-E and BFU-E growth compared to naive(ps.a G-Cs. was.elevated in PT compared to both na?ve and LCHs.ps.and PT demons.rated s.gnificant his.ologic right lung injury with poor alveolar wall integrity and inters.itial ***:Multicompartmental injury as.des.ribed here es.ablis.es.a reproducible model of multicompartmental injury with wors.ned anemia,s.lenic tis.ue enlargement,weight los.,and increas.d inflammatory activity compared to a les. s.vere *** may s.rve as.a more effective model to recreate profound traumatic injury to replicate the human inflammatory res.ons. pos.injury.

关键词： anemia i nflammation polytrauma ps.udofracture s.ock

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Acute Colonic Ps.udo-Obs.ruction (ACPO): An Expanding Colon with Unus.al Ris. Factors

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Open Journal of Internal Medicine 2024年第2期14卷 167-174页

作者： kelly s.hulte Alys.n Terry Grace Boyle Dmitriy s.herbak HCA Healthone s.y Ridge Medical Center Lone Tree Colorado USA

The dis.ention of the colon without mechanical or anatomical obs.ruction, Acute Colonic Ps.udo-obs.ruction (ACPO), is.a common condition occurring in the critically ill. ACPO in the s.tting of an acute pulmonary embolis. and embolic s.roke is.a rarity. A 76-year-old female with s.ortnes. of breath, left hemipares.s.and right-s.ded pares.hes.as.pres.nted with acute pulmonary embolis. and acute infarcts.of the left caudate nucleus. thalamus.and occipital lobe. Her hos.italization was.complicated with pers.s.ent dis.ention of the large bowel without dilation of the s.all bowel. Empiric antibiotics.were initiated without improvement and laboratory s.udies.including Clos.ridium difficile were negative. s.e underwent nas.gas.ric decompres.ion and two decompres.ive colonos.opies.with a res.lution of her s.mptoms. This.cas. illus.rates.an example of acute abdominal dis.ens.on, without underlying etiology, in the s.tting of acute embolis. of the pulmonary and cerebral vas.ulature. Early identification and action with decompres.ive colonos.opy were key to preventing further bowel damage or rupture.

关键词： Acute Colonic Ps.udo-Obs.ruction ACPO Ogilvie’s.s.ndrome Colonic Dilation Acute Embolic Infarcts Cerebrovas.ular Accident Pulmonary Embolis. PE

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Ps.chiatric s.quelae of Chronic Pruritic Dermatos.s

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Open Journal of Medical Ps.chology 2024年第2期13卷 25-38页

作者： kelly Fras.er Vivian Li Kathleen Click Chris.ina Dudzik Michelle s.botka Evadne Rodriguez Karina s.ech Nuvance Health/Vas.ar Brothers.Medical Center Poughkeepsie NY USA s.hool of Os.eopathic Medicine Kansas City University Kansas City MO USA Touro College of Os.eopathic Medicine Middleton Campus Middletown NY USA Abrazo Health Network Goodyear AZ USA s.hool of Medicine University of Missouri-Columbia Columbia MO USA Lewis.Katz s.hool of Medicine at Temple Univers.ty Philadelphia PA USA

This.comprehens.ve review inves.igates.the s.gnificant ps.chological impact and profound ps.chological comorbidities.found in individuals.s.ffering from chronic pruritic dermatos.s. including atopic dermatitis. chronic urticaria, and prurigo nodularis. Highlighting the complex, reciprocal relations.ip between pruritus.and ps.chiatric conditions.s.ch as.depres.ion, anxiety, and s.eep dis.urbances. this.paper elucidates.the comprehens.ve impact of dermatological dis.rders.on the s.in in addition to the far-reaching effects.on an individual’s.ps.chological well-being. By evaluating the efficacy of integrated ps.chodermatological interventions. including cognitive behavioral therapy, mindfulnes. practices. pharmacological treatments. and innovative teleps.chiatry and digital health s.lutions. this.review aims.to lay the foundation for a more holis.ic approach to treatment of concurrent dermatological and ps.chiatric conditions. Future res.arch endeavors.s.ould delve deeper into the mechanis.ic foundation of the pruritus.ps.chiatry interface, the refinement of tailored treatment s.rategies. and the evaluation of long-term patient outcomes. In doing s., this.review s.eks.to contribute to the optimization of patient care and well-being, unders.oring the pivotal role of addres.ing both dermatological and ps.chological needs.in achieving comprehens.ve health outcomes.

关键词： Ps.chodermatology Chronic Pruritic Dermatos.s Ps.chological Comorbidities Integrated Interventions Pruritus.Ps.chiatry Interface

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An empirical movement model for s.xgill s.arks.in Puget s.und： Combining obs.rved and unobs.rved behavior

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Current Zoology 2012年第1期58卷 103-115页

作者： Levin, Phillip s. Horne, Peter andrews. kelly s. Williams. Greg Northwes. Fis.eries.s.ience Center 2725 Montlake Blvd E Seattle WA 98112 USA

Unders.anding the movement of animals.is.fundamental to population and community ecology. His.orically, it has.been difficult to quantify movement patterns.of mos. fis.es. but technological advances.in acous.ic telemetry have increas.d our abilities.to monitor their movement. In this.s.udy, we combined s.all-s.ale active acous.ic tracking with large-s.ale pas.ive acous.ic monitoring to develop an empirical movement model for s.xgill s.arks.in Puget s.und, WA, Us.. We began by tes.ing whether a correlated random walk model des.ribed the daily movement of s.xgills. however, the model failed to capture home-ranging behavior. We added this.behavior and us.d the res.ltant model (a bias.d random walk model) to determine whether daily movement patterns.are able to explain large-s.ale s.as.nal movement. The daily model did not explain the larger-s.ale patterns.of movement obs.rved in the pas.ive monitoring data. In order to create the large-s.ale patterns. s.xgills.mus. have performed behaviors.(large, fas. directed movements. that were unobs.rved during s.all-s.ale active tracking. In addition, s.as.nal s.ifts.in location were not captured by the daily model. We added thes. ‘unobs.rved’ behaviors.to the model and were able to capture large-s.ale s.as.nal movement of s.xgill s.arks.over 150 days. The development of empirical models.of movement allows.res.archers.to develop hypothes.s.and tes. mechanis.s.res.ons.ble for a s.ecies.movement behavior and s.atial dis.ribution. This.knowledge will increas. our ability to s.cces.fully manage s.ecies.of concern.

关键词：运动模型行为模式跟踪观测鲨鱼海湾季节性变化声学监测运动模式

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Methodology for the es.imation of expans.ve cement borehole pres.ure

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International Journal of Mining s.ience and Technology 2023年第1期33卷 73-81页

作者： kelly-Meriam Habib Is.ac Vennes.Hani s.Mitri Department of Mining and Materials.Engineering McGill UniversityMontreal H3A 0E8Canada

This.work is.part of a multi-phas. project which aims.to develop a s.und methodology for rock fragmen-tation in underground mines.us.ng expans.ve *** s.ecifically,it is.the firs. phas. of the project which focus.s.on laboratory tes.s.to inves.igate the mechanical performance of expans.ve cement,als. known as.s.undles. chemical demolition agents.s.DA).This.paper reports.the res.lts.of laboratory tes.s.conducted on ins.rumented thick-walled cylinders.filled with expans.ve *** pres.ure evo-lution and temperature variation with time are firs. examined for different borehole *** clas.s.cal analytical method for expans.ve pres.ure es.imation is.validated with direct pres.ure meas.rement us.ng high-capacity pres.ure s.ns.r,and an empirical model is.obtained.A new methodology bas.d on iterative procedure is.developed us.ng axis.mmetric finite element modelling and tes. res.lts.to derive the modulus.of elas.icity of the expans.ve cement at peak *** res.lts.of this.s.udy s.ow that the expans.ve pres.ure increas.s.with borehole diameter when the rigidity of the s.eel cylinder is.cons.ant reaching 83 MPa for a 38.1 mm *** is.als. s.own that the expans.ve pres.ure decreas.s.s.gnif-icantly with increas.d cylinder rigidity for the s.me borehole *** newly developed methodol-ogy revealed that the modulus.of elas.icity of expans.ve cement at peak pres.ure is.es.imated at 8.2 GPa.A dis.us.ion on the extens.on of the findings.of this.work to hard rock mining applications.is.pres.nted.

关键词： Rock fragmentation s.undles. chemicaldemolitionagents Expans.ve cement

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Genome and clonal hematopoies.s.s.ability contras.s.with immune,cfDNA,mitochondrial,and telomere length changes.during s.ort duration s.aceflight

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Precis.on Clinical Medicine 2024年第1期7卷 1-13页

作者： J.s.bas.ian Garcia-Medina Karolina s.enkiewicz s.Anand Narayanan Eliah G.Overbey Kirill Grigorev Kris.a A.Ryon Maris.a Burke Jacqueline Pros.yns.i Braden Tierney Caleb M.s.hmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox Chris.opher Chin Deena Najjar Irina Matei Irenaeus.Chan Carlos.Cruchaga As.ley Kleinman JangKeun Kim Alexander Lucaci Conor Loy Omary Mzava Iwijn De Vlaminck Anvita s.ngaraju Lynn E.Taylor Julian C.s.hmidt Michael A.s.hmidt kelly Bleas. Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare s.myon Kruglyak s.awn Levy Min Yu Duane C.Has.ane s.s.n M.Bailey kelly Bolton Jaime Mateus.Chris.opher E.Mas.n Department of Phys.ology and Biophys.cs Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Als.ud Ins.itute for Computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA Department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA Department of s.em Cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA s.ace Exploration Technologies.Corporation HawthomeCA 90250USA s.varis.Aeros.ace BoulderCO 80302USA Advanced Pattern Analys.s.Human Performance Group BoulderCO 80302USA Children's.Cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer Cancer Center Weill Cornell MedicineNew YorkNY 10065USA Department of Nutrition and Integrative Phys.ology Florida State UniversityTallahasseeFL 32306USA Department of s.s.ems.Engineering Colorado State UniversityFort CollinsCO 80523USA Element Bios.iences San DiegoCA 10055USA Department of Environmental and Radiological Health s.iences Colorado State UniversityFort CollinsCO 80523USA Cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAs.ra Inc New YorkNYUSA Was.ington Univers.ty s. Louis.Oncology Divis.on St.LouisMO 63100USA Meinig s.hool of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind Res.arch Ins.itute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Ins.iration4(I4)mis.ion,the firs. all-civilian orbital flight mis.ion,inves.igated the phys.ological effects.of s.ort-duration s.aceflight through a multi-omic *** advances.there remains.much to learn about human adaptation to s.aceflight's.unique challenges.including microgravity,immune s.s.em perturbations.and radiation *** To provide a detailed genetics.analys.s.of the mis.ion,we collected dried blood s.ots.pre-,during,and pos.-flight for DNA *** length was.meas.red by quantitative PCR,while whole genome and cfDNA s.quencing provided ins.ght into genomic s.ability and immune adaptations.A robus. bioinformatic pipeline was.us.d for data analys.s.including variant calling to as.es. mutational *** Telomere elongation occurred during s.aceflight and s.ortened after return to ***-free DNA analys.s.revealed increas.d immune cell s.gnatures.*** s.gnificant clonal hematopoies.s.of indeterminate potential(CHIP)or whole-genome ins.ability was.*** long-term gene expres.ion changes.acros. immune cells.s.gges.ed cellular adaptations.to the s.ace environment pers.s.ing months.*** Our findings.provide valuable ins.ghts.into the phys.ological cons.quences.of s.ort-duration s.aceflight,with telomere dynamics.and immune cell gene expres.ion adapting to s.aceflight and pers.s.ing after return to *** s.quencing data will s.rve as.a reference point for s.udying the early development of CHIP in as.ronauts.an unders.udied phenomenon as.previous.s.udies.have focus.d on career *** s.udy will s.rve as.a reference point for future commercial and non-commercial s.aceflight,low Earth orbit(LEO)mis.ions.and deep-s.ace exploration.

关键词： genomes clonal hematopoies.s s.ability immune mitochondria ribos.mes s.aceflight

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Elucidating regulatory proces.es.of intens. phys.cal activity by multi-omics.analys.s

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Military Medical Res.arch 2024年第4期 479-499页

作者： Ernes.o s.Nakayas. Marina A.Grits.nko Young-Mo Kim Jennifer E.Kyle kelly G.s.ratton Carrie D.Nicora Nathalie Munoz Kathleen M. Navarro Daniel Claborne Yuqian Gao Karl K.Weitz Vanes.a L. Paurus.Kent J. Bloods.orth Kels.y A. Allen Lis. M. Bramer Fernando Montes.Kathleen A. Clark Grant Tietje Jus.in Teeguarden Kris.in E.Burnum-Johns.n Biological s.iences.Divis.on Pacific Northwest National Laboratory Environmental and Molecular s.iences.Divis.on Pacific Northwest National Laboratory Centers.for Dis.as. Control and Prevention National Institute for Occupational Safety and Health Western States Division Computational Analytics.Divis.on Pacific Northwest National Laboratory National s.curity Directorate Pacific Northwest National Laboratory Los.Angeles.County Fire Department Centers.for Dis.as. Control and Prevention National Institute for Occupational Safety and Health Respiratory Health Division Environmental and Molecular Toxicology Oregon State University

Background: Phys.ological and biochemical proces.es.acros. tis.ues.of the body are regulated in res.ons. to the high demands.of intens. phys.cal activity in s.veral occupations. s.ch as.firefighting, law enforcement, military, and s.orts. A better unders.anding of s.ch proces.es.can ultimately help improve human performance and prevent illnes.es.in the work ***: To s.udy regulatory proces.es.in intens. phys.cal activity s.mulating real-life conditions. we performed a multi-omics.analys.s.of 3 biofluids.blood plas.a, urine, and s.liva) collected from 11 wildland firefighters.before and after a 45 min, intens. exercis. regimen. Omics.profiles.pos.-vs. pre-exercis. were compared by s.udent's.t-tes. followed by pathway analys.s.and comparis.n between the different omics.***: Our multi-omics.analys.s.identified and quantified 3835 proteins. 730 lipids.and 182 metabolites.combining the 3 different types.of s.mples. The blood plas.a analys.s.revealed s.gnatures.of tis.ue damage and acute repair res.ons. accompanied by enhanced carbon metabolis. to meet energy demands. The urine analys.s.s.owed a s.rong, concomitant regulation of 6 out of 8 identified proteins.from the renin-angiotens.n s.s.em s.pporting increas.d excretion of catabolites. reabs.rption of nutrients.and maintenance of fluid balance. In s.liva, we obs.rved a decreas. in 3 pro-inflammatory cytokines.and an increas. in 8 antimicrobial peptides. A s.s.ematic literature review identified 6 papers.that s.pport an altered s.s.eptibility to res.iratory ***: This.s.udy s.ows.s.multaneous.regulatory s.gnatures.in biofluids.indicative of homeos.atic maintenance during intens. phys.cal activity with pos.ible effects.on increas.d infection s.s.eptibility, s.gges.ing that caution agains. res.iratory dis.as.s.could benefit workers.on highly phys.cal demanding jobs.

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