!function(){"use strict";var e={d:function(r,t){for(var n in t)e.o(t,n)&&!e.o(r,n)&&Object.defineProperty(r,n,{enumerable:!0,get:t[n]})}};e.g=function(){if("object"==typeof globalThis)return globalThis;try{return this||new Function("return this")()}catch(e){if("object"==typeof window)return window}}(),e.o=function(e,r){return Object.prototype.hasOwnProperty.call(e,r)},e.g.window.addEventListener("DOMContentLoaded",(()=>{r()}));const r=function(){const e=""!==document.referrer?document.referrer:document.URL,r=document.querySelectorAll('a[href*="ref=pmcTrackonomicsReferrer"]');for(let t=0;t<r.length;t++)r[t].href=r[t].href.replace("ref=pmcTrackonomicsReferrer","ref="+encodeURIComponent(e))}}();;
!function(){"use strict";function a(a){this.time=a.time,this.target=a.target,this.rootBounds=a.rootBounds,this.boundingClientRect=a.boundingClientRect,this.intersectionRect=a.intersectionRect||i(),this.isIntersecting=!!a.intersectionRect;var b=this.boundingClientRect,c=b.width*b.height,d=this.intersectionRect,e=d.width*d.height;c?this.intersectionRatio=Number((e/c).toFixed(4)):this.intersectionRatio=this.isIntersecting?1:0}function b(a,b){var c=b||{};if("function"!=typeof a)throw new Error("callback must be a function");if(c.root&&1!=c.root.nodeType)throw new Error("root must be an Element");this._checkForIntersections=d(this._checkForIntersections.bind(this),this.THROTTLE_TIMEOUT),this._callback=a,this._observationTargets=[],this._queuedEntries=[],this._rootMarginValues=this._parseRootMargin(c.rootMargin),this.thresholds=this._initThresholds(c.threshold),this.root=c.root||null,this.rootMargin=this._rootMarginValues.map(function(a){return a.value+a.unit}).join(" ")}function c(){return window.performance&&performance.now&&performance.now()}function d(a,b){var c=null;return function(){c||(c=setTimeout(function(){a(),c=null},b))}}function e(a,b,c,d){"function"==typeof a.addEventListener?a.addEventListener(b,c,d||!1):"function"==typeof a.attachEvent&&a.attachEvent("on"+b,c)}function f(a,b,c,d){"function"==typeof a.removeEventListener?a.removeEventListener(b,c,d||!1):"function"==typeof a.detatchEvent&&a.detatchEvent("on"+b,c)}function g(a,b){var c=Math.max(a.top,b.top),d=Math.min(a.bottom,b.bottom),e=Math.max(a.left,b.left),f=Math.min(a.right,b.right),g=f-e,h=d-c;return g>=0&&h>=0&&{top:c,bottom:d,left:e,right:f,width:g,height:h}}function h(a){var b;try{b=a.getBoundingClientRect()}catch(c){}return b?(b.width&&b.height||(b={top:b.top,right:b.right,bottom:b.bottom,left:b.left,width:b.right-b.left,height:b.bottom-b.top}),b):i()}function i(){return{top:0,bottom:0,left:0,right:0,width:0,height:0}}function j(a,b){for(var c=b;c;){if(c==a)return!0;c=k(c)}return!1}function k(a){var b=a.parentNode;return b&&11==b.nodeType&&b.host?b.host:b&&b.assignedSlot?b.assignedSlot.parentNode:b}if("object"==typeof window){if("IntersectionObserver"in window&&"IntersectionObserverEntry"in window&&"intersectionRatio"in window.IntersectionObserverEntry.prototype)return void("isIntersecting"in window.IntersectionObserverEntry.prototype||Object.defineProperty(window.IntersectionObserverEntry.prototype,"isIntersecting",{get:function(){return this.intersectionRatio>0}}));var l=window.document,m=[];b.prototype.THROTTLE_TIMEOUT=100,b.prototype.POLL_INTERVAL=null,b.prototype.USE_MUTATION_OBSERVER=!0,b.prototype.observe=function(a){var b=this._observationTargets.some(function(b){return b.element==a});if(!b){if(!a||1!=a.nodeType)throw new Error("target must be an Element");this._registerInstance(),this._observationTargets.push({element:a,entry:null}),this._monitorIntersections(),this._checkForIntersections()}},b.prototype.unobserve=function(a){this._observationTargets=this._observationTargets.filter(function(b){return b.element!=a}),this._observationTargets.length||(this._unmonitorIntersections(),this._unregisterInstance())},b.prototype.disconnect=function(){this._observationTargets=[],this._unmonitorIntersections(),this._unregisterInstance()},b.prototype.takeRecords=function(){var a=this._queuedEntries.slice();return this._queuedEntries=[],a},b.prototype._initThresholds=function(a){var b=a||[0];return Array.isArray(b)||(b=[b]),b.sort().filter(function(a,b,c){if("number"!=typeof a||isNaN(a)||0>a||a>1)throw new Error("threshold must be a number between 0 and 1 inclusively");return a!==c[b-1]})},b.prototype._parseRootMargin=function(a){var b=a||"0px",c=b.split(/\s+/).map(function(a){var b=/^(-?\d*\.?\d+)(px|%)$/.exec(a);if(!b)throw new Error("rootMargin must be specified in pixels or percent");return{value:parseFloat(b[1]),unit:b[2]}});return c[1]=c[1]||c[0],c[2]=c[2]||c[0],c[3]=c[3]||c[1],c},b.prototype._monitorIntersections=function(){this._monitoringIntersections||(this._monitoringIntersections=!0,this.POLL_INTERVAL?this._monitoringInterval=setInterval(this._checkForIntersections,this.POLL_INTERVAL):(e(window,"resize",this._checkForIntersections,!0),e(l,"scroll",this._checkForIntersections,!0),this.USE_MUTATION_OBSERVER&&"MutationObserver"in window&&(this._domObserver=new MutationObserver(this._checkForIntersections),this._domObserver.observe(l,{attributes:!0,childList:!0,characterData:!0,subtree:!0}))))},b.prototype._unmonitorIntersections=function(){this._monitoringIntersections&&(this._monitoringIntersections=!1,clearInterval(this._monitoringInterval),this._monitoringInterval=null,f(window,"resize",this._checkForIntersections,!0),f(l,"scroll",this._checkForIntersections,!0),this._domObserver&&(this._domObserver.disconnect(),this._domObserver=null))},b.prototype._checkForIntersections=function(){var b=this._rootIsInDom(),d=b?this._getRootRect():i();this._observationTargets.forEach(function(e){var f=e.element,g=h(f),i=this._rootContainsTarget(f),j=e.entry,k=b&&i&&this._computeTargetAndRootIntersection(f,d),l=e.entry=new a({time:c(),target:f,boundingClientRect:g,rootBounds:d,intersectionRect:k});j?b&&i?this._hasCrossedThreshold(j,l)&&this._queuedEntries.push(l):j&&j.isIntersecting&&this._queuedEntries.push(l):this._queuedEntries.push(l)},this),this._queuedEntries.length&&this._callback(this.takeRecords(),this)},b.prototype._computeTargetAndRootIntersection=function(a,b){if("none"!=window.getComputedStyle(a).display){for(var c=h(a),d=c,e=k(a),f=!1;!f;){var i=null,j=1==e.nodeType?window.getComputedStyle(e):{};if("none"==j.display)return;if(e==this.root||e==l?(f=!0,i=b):e!=l.body&&e!=l.documentElement&&"visible"!=j.overflow&&(i=h(e)),i&&(d=g(i,d),!d))break;e=k(e)}return d}},b.prototype._getRootRect=function(){var a;if(this.root)a=h(this.root);else{var b=l.documentElement,c=l.body;a={top:0,left:0,right:b.clientWidth||c.clientWidth,width:b.clientWidth||c.clientWidth,bottom:b.clientHeight||c.clientHeight,height:b.clientHeight||c.clientHeight}}return this._expandRectByRootMargin(a)},b.prototype._expandRectByRootMargin=function(a){var b=this._rootMarginValues.map(function(b,c){return"px"==b.unit?b.value:b.value*(c%2?a.width:a.height)/100}),c={top:a.top-b[0],right:a.right+b[1],bottom:a.bottom+b[2],left:a.left-b[3]};return c.width=c.right-c.left,c.height=c.bottom-c.top,c},b.prototype._hasCrossedThreshold=function(a,b){var c=a&&a.isIntersecting?a.intersectionRatio||0:-1,d=b.isIntersecting?b.intersectionRatio||0:-1;if(c!==d)for(var e=0;e<this.thresholds.length;e++){var f=this.thresholds[e];if(f==c||f==d||c>f!=d>f)return!0}},b.prototype._rootIsInDom=function(){return!this.root||j(l,this.root)},b.prototype._rootContainsTarget=function(a){return j(this.root||l,a)},b.prototype._registerInstance=function(){m.indexOf(this)<0&&m.push(this)},b.prototype._unregisterInstance=function(){var a=m.indexOf(this);-1!=a&&m.splice(a,1)},window.IntersectionObserver=b,window.IntersectionObserverEntry=a}}();;