{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:32:39Z","timestamp":1787164359515,"version":"build-2736575974"},"reference-count":95,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Acute low oxygen exposure (hypoxia) elicits a hypoxic ventilatory response (HVR), which increases ventilation and mitigates hypoxaemia. During sustained exposure to hypoxia, ventilatory acclimatization increases peripheral chemoreflex (HVR) sensitivity or chemoreflex loop gain (LG). Although increased ventilation protects oxygenation, increased LG contributes to ventilatory instability during sleep (central sleep apnoea; CSA). The HVR is highly variable between individuals, and the impact of sex on HVR variability and LG is unclear. At low altitude (1100\u00a0m), we aimed to characterize a novel breath hold method to quantify LG using a standardized series of short (\u223c10\u00a0s), voluntary, end\u2010expiratory breath holds (EEBH), using a background of steady\u2010state normobaric inspired hyperoxia (fraction of inspired oxygen; \u00a0=\u00a01.0), normoxia (i.e., ambient air; \u00a0=\u00a00.21) and hypoxia (\u00a0=\u00a00.14; equivalent to \u223c4300\u00a0m altitude). Further, we investigated sex differences in LG during differential oxygen exposure using this novel EEBH protocol to quantify LG. We hypothesized that (a) LG magnitude would follow an inverse oxygen\u2010dependent pattern with each inspired gas condition, and (b) that males would have higher LG than females. We recruited 36 healthy participants (18 females; 18 males). We found (a) a graded, inverse oxygen\u2010dependent effect on LG magnitude (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.0001), and (b) a sex\u2010specific effect, whereby males had significantly larger LG magnitudes than females, but only in steady\u2010state inspired hypoxia (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    &lt;\u00a00.032). Our EEBH protocol illustrates an intrinsic sex difference in chemoreflex LG in hypoxia, which may underlie known sex differences in CSA at high altitude and in heart failure populations.\n                  <\/jats:p>","DOI":"10.1113\/ep092285","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:40:14Z","timestamp":1753713614000},"page":"1397-1412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sex differences in loop gain measured via superimposed end\u2010expiratory breath holds and inspired steady\u2010state hypoxia"],"prefix":"10.1113","volume":"111","author":[{"given":"Benjamin W. L.","family":"MacKenzie","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D. J.","family":"Strzalkowski","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7102-4235","authenticated-orcid":false,"given":"Trevor A.","family":"Day","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Science and Technology Mount Royal University  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01178.2006"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.05.020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1986.60.6.1894"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.650796"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.4.1683"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.06.006"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1999.86.5.1519"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2005.04.002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200208-876OC"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00363.2021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202211-918OC"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.02.014"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00697"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/146.6.1394"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085764"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00165.2017"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.06.006"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201212-2250ED"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.14-0317"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2018.00132"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00453.2010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.06.007"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00892.2003"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0003-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01126.2013"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2008"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.028696"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2011.04.009"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.277210"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270061"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP281635"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2020.34.s1.01775"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.024103"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-024-00731-5"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168930"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.07.004"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.08.001"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11325-015-1290-z"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.284521"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.031186"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2011.06.010"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00604.2023"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsac113"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2013.tb00482.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12121758"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4143-12.2013"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e34491"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(00)00157-2"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2005.07.001"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010664"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11102869"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.008615"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1183\/20734735.000318"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.12012"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00727.2011"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm\/144.3_Pt_1.481"},{"issue":"2","key":"e_1_2_9_58_1","first-page":"00507","article-title":"End\u2010tidal carbon dioxide tension is a reliable surrogate of arterial carbon dioxide tension across different oxygen, carbon dioxide and barometric pressures","volume":"9","author":"Manferdelli G.","year":"2023","journal-title":"European Respiratory Journal Open Research"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2014.082826"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.266221"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-021-04864-5"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.6.1872"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP276206"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.09.002"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00484.2014"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00864.2002"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.3.262"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.9.1183"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.03.00045402"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP284767"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1111\/resp.12927"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP285427"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00418.2021"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085498"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2013.04.020"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5687(98)00026-7"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-023-01954-6"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(90)90027-V"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2019.0063"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00035.2013"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2017.05.005"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/710537"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP085366"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1097\/JES.0b013e31817be7f0"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.162.6.2002024"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2006.05.006"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000266974.84590.d2"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1997.83.5.1706"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2009"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2016.10.005"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.2298"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2008.05.019"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00371.2018"},{"issue":"4","key":"e_1_2_9_94_1","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1152\/jappl.1983.54.4.874","article-title":"Sexual influence on the control of breathing","volume":"54","author":"White D. P.","year":"1983","journal-title":"Journal of Applied Physiology: Respiratory, Environmental and Exercise Physiology"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1987.63.1.401"},{"key":"e_1_2_9_96_1","first-page":"194","article-title":"Effect of sleep on breathing\u2014Why recurrent apneas are only seen during sleep","volume":"4","author":"Xie A.","year":"2012","journal-title":"Journal of Thoracic Disease"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP092285","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP092285","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP092285","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:05:26Z","timestamp":1773003926000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP092285"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":95,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1113\/EP092285"],"URL":"https:\/\/doi.org\/10.1113\/ep092285","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,28]]},"assertion":[{"value":"2025-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}