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  • Profile picture of Bojesen Meyers

    Bojesen Meyers posted an update a month ago

    The reduction of the proliferative rates was attributed to the induction of ROS triggered apoptosis which was associated with activation of Caspase-3, upregulation of Bax and suppression of Bcl-2. Voacangine induced G2/M cell cycle arrest in a dose-dependent manner. Additionally, the anticancer effects of Voacangine on oral cancer cells were exerted through the inhibition of PI3K/AKT signaling cascade.

    Taken all together, we conclude that Voacangine is a potent anticancer molecule and may be utilized for the development of systemic therapy for oral cancer.

    Taken all together, we conclude that Voacangine is a potent anticancer molecule and may be utilized for the development of systemic therapy for oral cancer.

    This study aimed to observe the effect of neo-adjuvant chemotherapy on the improvement of oral cancer patients and investigate the predictive value of miR-182 on its efficacy.

    A total of 143 patients with advanced oral cancer admitted to Yidu Central Hospital of Weifang from September 2015 to July 2017 formed the study group. Among them, there were 62 cases in the control group (surgery+postoperative radiotherapy) and 81 cases in the study group (preoperative neo-adjuvant chemotherapy+surgery+postoperative radiotherapy). The treatment effect and adverse reactions of patients were compared between the two groups. RT-PCR was used to detect the expression levels of serum miR-182 of patients before and after treatment. The 1-year survival of patients in the two groups was recorded and compared by follow-up.

    The total effective rate of patients in the study group was significantly higher than that of patients in the control group (p<0.05). The incidence of adverse reactions of patients in the study group ioration of oral cancer and is a good indicator for predicting the treatment efficacy of patients with oral cancer.

    Oral cancer is one among the devastating types of malignancies and imposes tremendous disease burden on humans. This study was undertaken to investigate the anticancer properties of a plant-derived flavanone, Blumeatin, against human oral cancer cells. Additionally, this study also attempted to unreveal the molecular mechanisms responsible for the anticancer properties of this molecule.

    MTT assay was used for the assessment of cell viability. Transwell and wound healing assays were used for the determination of cell invasion and migration, respectively. Comet assay was used for the determination of cell viability. Transmission electron microscopy (TEM) analysis was done to assess the induction of autophagy. The protein expression was determined by western blot analysis.

    Blumeatin inhibited the growth of SCC-4 oral cancer cells with minimal cytotoxic effects against the normal hTRET-OME cells. The flow cytometric analysis showed that Blumeatin triggers DNA damage in the SCC-4 cells. Blumeatin also activated autophagy in SCC-4 cells which was accompanied with upregulation of LC3B and Beclin 1. This molecule also increased ROS and decreased the MMP levels in human SCC-4 cells. The effects of Blumeatin were also examined on the migration and invasion of the SCC-4 cells and it was revealed that the molecule suppresses both migration and invasion of the SCC-4 oral cancer cells.

    This study indicates that Blumeatin exhibits potent anticancer effects and points towards its use in the development of a new systemic therapy for oral cancer.

    This study indicates that Blumeatin exhibits potent anticancer effects and points towards its use in the development of a new systemic therapy for oral cancer.

    To investigate the efficacy of second-line regimen in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), and to analyze relevant prognostic factors.

    The clinical data of 105 patients with relapsed or refractory DLBCL admitted and treated from July 2004 to June 2016 were retrospectively reviewed, the response rate after chemotherapy was assessed, and overall survival (OS) was calculated using Kaplan-Meier method. Moreover, Cox regression model was adopted for multivariate analysis, so as to find the independent prognostic factors influencing patient’s OS.

    Among the 105 patients, there were 67 males and 38 females, with a median age of 57.54 years. There were 31 cases of CR and 21 cases of PR, and the objective response rate (ORR) was 49.5%. In addition, early progression or recurrence <12 months of relapsed or refractory DLBCL and high-risk international prognostic index (IPI) were the negative factors for response rate to chemotherapy. At the end of follow-up, the median OS of thesk IPI is an independent risk factor influencing the survival of patients with relapsed or refractory DLBCL, and response rate after chemotherapy is an independent prognostic indicator for extending the OS of patients.

    To explore the efficacy of different regimens in nasal natural killer (NK)/T-cell lymphoma (NNKTL) and their effects on the serum inflammation and prognosis of patients.

    146 NNKTL patients admitted to and treated in the Oncology Department of our hospital from January 2010 to December 2014 were randomly enrolled and divided into chemotherapy group (group A) and concurrent chemoradiotherapy group (group B). The expression levels of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) before and after treatment were detected, the short-term efficacy was followed up and analyzed, and the correlation between the two was statistically analyzed.

    In group A and group B, the total short-term effective rate was 71.87% and 84.97%, the 5-year overall survival (OS) rate was 39.9% and 66.2%, and the progression-free survival (PFS) rate was 18.1% and 46.9%, respectively. Decursin Treatment regimens, clinical stage, the presence of B symptoms and lactate dehydrogenase (LDH) level were independent factors related to prognosis, and the remission rate after the first-course chemotherapy was an independent factor unrelated to prognosis. After treatment, there was no significant difference in the IL-2 level between the two groups of patients before and after treatment. The expression level of TNF-α after treatment was reduced compared with that before treatment, and the reduction was more obvious in group B.

    The short-term efficacy of concurrent chemoradiotherapy favors NNKTL, and the therapy can reduce the expression level of TNF-α.

    The short-term efficacy of concurrent chemoradiotherapy favors NNKTL, and the therapy can reduce the expression level of TNF-α.

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!function(e,t){"object"==typeof exports&&"undefined"!=typeof module?t(exports):"function"==typeof define&&define.amd?define(["exports"],t):t((e="undefined"!=typeof globalThis?globalThis:e||self).version={})}(this,(function(exports){"use strict";function __awaiter(e,t,n,i){return new(n||(n=Promise))((function(s,a){function o(e){try{d(i.next(e))}catch(e){a(e)}}function r(e){try{d(i.throw(e))}catch(e){a(e)}}function d(e){var t;e.done?s(e.value):(t=e.value,t instanceof n?t:new n((function(e){e(t)}))).then(o,r)}d((i=i.apply(e,t||[])).next())}))}var Blocking;"function"==typeof SuppressedError&&SuppressedError,function(e){e.PENDING="pending",e.NONE="none",e.BLOCKED="blocked",e.ALLOWED="allowed"}(Blocking||(Blocking={}));class Adblock{constructor(e){this.state=Blocking.PENDING,this._mocked=!1,e?(this.state=e,this._mocked=!0):this.state=Blocking.ALLOWED}inject(){return __awaiter(this,void 0,void 0,(function*(){}))}hasAdblocker(){if(void 0===window.google)return!0;const e=document.querySelectorAll("style");return Array.from(e).some((e=>!!e.innerHTML.includes("adblockkey")))}handleAdblocked(){this.removeAdblockKey(),this.state=Blocking.BLOCKED}removeAdblockKey(){var e;null===(e=document.documentElement.dataset)||void 0===e||delete e.adblockkey}get isBlocked(){return this.state===Blocking.BLOCKED}get isAllowed(){return this.state===Blocking.ALLOWED}toContext(){return{user_has_ad_blocker:null,is_ad_blocked:null}}}const OBFUSCATING_BASE_64_PREFIX="UxFdVMwNFNwN0wzODEybV",encode=e=>OBFUSCATING_BASE_64_PREFIX+btoa(unescape(encodeURIComponent(JSON.stringify(e))));function decode$1(e){return JSON.parse(decodeURIComponent(escape(atob(e.replace(OBFUSCATING_BASE_64_PREFIX,"")))))}var version="0.8.1";const APP_ENV="production",TRACKING_DOMAIN="https://click-use1.bodis.com/",SALES_JS_URL="https://parking.bodiscdn.com/js/inquiry.js",GOOGLE_CAF_TIMEOUT_SCRIPTS="0",GOOGLE_CAF_TIMEOUT_CALLBACKS="0",GOOGLE_MV3_URL_PARAMS="abp=1&bodis=true",APP_VERSION=version,COOKIE_CONSENT_JS_URL="",AFD_CHEQ_LOAD_PERCENTAGE="30",isLocal=(e=!0)=>"production"!==APP_ENV;function log(...e){}const FIND_DOMAIN_URL="_fd",getFindDomain=(e="",t=!1,n="")=>{const i=n||window.location.search,s=`${e}/${FIND_DOMAIN_URL}${i}`,a=e?"include":"same-origin",o=Object.assign({Accept:"application/json","Content-Type":"application/json"},t?{"X-HOST":window.location.host}:{});return fetch(s,{method:"POST",headers:o,credentials:a}).then((e=>e.text())).then(decode$1)};var ZeroClickReasons;!function(e){e.CAF_TIMEDOUT="caf_timedout",e.CAF_ADLOAD_FAIL_RS="caf_adloadfail_rs",e.CAF_ADLOAD_FAIL_ADS="caf_adloadfail_ads",e.DISABLED_GB="disabled_gb",e.DISABLED_AB="disabled_ab",e.DISABLED_DS="disabled_ds",e.AD_BLOCKED="ad_blocked",e.PREFERRED="preferred"}(ZeroClickReasons||(ZeroClickReasons={}));const getZeroClick=e=>__awaiter(void 0,void 0,void 0,(function*(){const t=Object.assign(Object.assign({},e),{type:"zc_fetch"});return fetch("/_zc",{method:"POST",body:JSON.stringify({signature:encode(t)}),headers:{Accept:"application/json","Content-Type":"application/json"}}).then((e=>__awaiter(void 0,void 0,void 0,(function*(){try{return decode$1(yield e.text())}catch(e){return{}}}))))})),waiter=(e,t)=>new Promise((n=>{t(e),e<=0&&n();let i=e;const s=()=>{i>0?(i-=1,t(i),setTimeout(s,1e3)):n()};s()})),decode=()=>JSON.parse(atob(window.park||""));var PAGE_STYLES='* {\n font-smoothing: antialiased;\n -webkit-font-smoothing: antialiased;\n -moz-osx-font-smoothing: grayscale;\n}\n\nhtml, body {\n width: 100%;\n margin: 0;\n}\n\nhtml {\n background-color: #2B2B2B;\n height: 100%;\n}\n\nbody {\n min-height: 90%;\n font-family: Arial, sans-serif;\n letter-spacing: 1.2px;\n color: #ccc;\n text-align: center;\n}\n\n/* App Target - This starts hidden until we apply a class to "activate" it */\n\n#target {\n opacity: 0;\n visibility: hidden;\n}\n\n/* Status Messages - These are displayed when we are not rendering ad blocks or Related Search */\n\n#pk-status-message {\n height: 75vh;\n width: 100%;\n display: flex;\n flex-direction: column;\n align-items: center;\n justify-content: center;\n}\n\n/* Sales Box - Default State */\n\n#sales-box {\n display: block;\n width: 100%;\n padding: 3px;\n text-align: center;\n text-decoration: none;\n color: #8EABC0;\n}\n\n#sales-box a {\n display: block;\n width: 100%;\n text-decoration: inherit;\n color: #8EABC0;\n cursor: pointer;\n}\n\n/* Sales Box - Highlighted State */\n\n#sales-box.is-highlighted {\n position: relative;\n z-index: 1;\n background: #032438 linear-gradient(to top, #044368 0%, #000 100%);\n box-shadow: 0 0 15px 0 #000;\n border-bottom: 3px solid #262626;\n}\n\n#sales-box.is-highlighted a {\n line-height: 1.3;\n display: inline-block;\n font-size: 18px;\n color: #fff;\n text-shadow: 1px 1px 0 rgba(0, 0, 0, 0.5);\n background: none;\n}\n\n/* Ellipsis Loader */\n\n.pk-loader {\n display: inline-block;\n position: relative;\n width: 80px;\n height: 80px;\n}\n\n.pk-loader div {\n position: absolute;\n top: 33px;\n width: 13px;\n height: 13px;\n border-radius: 50%;\n background: #ccc;\n animation-timing-function: cubic-bezier(0, 1, 1, 0);\n}\n\n.pk-loader div:nth-child(1) {\n left: 8px;\n animation: pk-anim-1 0.6s infinite;\n}\n\n.pk-loader div:nth-child(2) {\n left: 8px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(3) {\n left: 32px;\n animation: pk-anim-2 0.6s infinite;\n}\n\n.pk-loader div:nth-child(4) {\n left: 56px;\n animation: pk-anim-1 0.6s infinite;\n animation-direction: reverse;\n}\n\n.pk-loader-text {\n position: fixed;\n font-size: 12px;\n right: 20px;\n bottom: 20px;\n font-weight: lighter;\n}\n\n/* Utilities */\n\n.pk-message-title {\n font-size: 2em;\n font-weight: bold;\n}\n\n.pk-page-ready {\n opacity: 1 !important;\n visibility: visible !important;\n}\n\n.hide-sales-banner > #sales-banner {\n display: none;\n}\n\n@media only screen and (max-width: 600px) {\n .hidden-xs {\n opacity: 0;\n visibility: hidden;\n }\n}\n\n/* Animation */\n\n@keyframes pk-anim-1 {\n 0% {\n transform: scale(0);\n }\n 100% {\n transform: scale(1);\n }\n}\n\n@keyframes pk-anim-2 {\n 0% {\n transform: translate(0, 0);\n }\n 100% {\n transform: translate(24px, 0);\n }\n}\n';const APP_TARGET="#target",MESSAGE_TARGET="main",MESSAGE_SELECTOR="#pk-status-message",PAGE_READY_CLASS="pk-page-ready",MESSAGE_TEMPLATE='
';class Renderer{constructor(e){this._domIsReady=!1,this.revealPage=()=>{this.domNode&&this.domNode.classList.add(PAGE_READY_CLASS)},this.hideSalesBanner=()=>{this.domNode.classList.add("hide-sales-banner")},this.revealSalesBanner=()=>{this.domNode.classList.remove("hide-sales-banner")},this.injectMetaDescription=e=>{if(!e||0===e.length)return;window.document.title=e;const t=document.createElement("meta");t.setAttribute("name","description"),t.setAttribute("content",`See relevant content for ${e}`),document.getElementsByTagName("head")[0].appendChild(t)},this.domNode=document.querySelector(e)}get domIsReady(){return this._domIsReady}set domIsReady(e){this._domIsReady=e,e&&this.injectStyles(PAGE_STYLES)}message(e,t=""){if(this.injectMessage(MESSAGE_TEMPLATE),this.domNode){const t=this.domNode.querySelector(MESSAGE_SELECTOR);t&&(t.innerHTML=e)}t&&this.injectMetaDescription(t)}injectMessage(e){const t=document.querySelector(MESSAGE_TARGET);t?t.innerHTML=e:this.domNode&&(this.domNode.innerHTML=e)}salesBanner(e){if(!e)return;const{href:t,position:n,message:i,theme:s,status:a}=e,o=document.createElement("div"),r=n||"",d="HIGHLIGHT"===s?"is-highlighted":"";o.innerHTML=t?`\n
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\n `:`\n
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\n `,"BOTTOM"===n?(o.style.marginTop="30px",document.body.appendChild(o)):document.body.prepend(o)}loading(e){let t="a few";e>0&&(t=`${e}`),this.message(`\n
\n
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\n \n `)}adBlockMessage(){this.message("\n

Ad block detected

\n Please disable your ad blocker and reload the page.\n ")}errorParkingUnavailable(){this.message("\n

An Error Occurred

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Parking is currently unavailable. We'll be right back.

\n ")}errorParkingServicesDisabled(){this.message("\n

An Error Occurred

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Services for this domain name have been disabled.

\n ")}errorParkingNoSponsors(e){this.message(`\n
\n No sponsors\n
\n \n ${window.location.hostname} currently does not have any sponsors for you.\n \n `,e)}imprint(e){if(!e)return;const t=document.querySelector("#imprint-text");t&&(t.innerHTML=e.replace(/(?:\r\n|\r|\n)/g,"
"))}injectStyles(e){if(!e)return;const t=document.createElement("style");t.innerHTML=e.toString(),document.head.appendChild(t)}injectScript(e){if(!e)return;const t=document.createElement("script");t.type="text/javascript",t.src=e,document.body.appendChild(t)}injectJS(js){js&&0!==js.length&&eval(js)}injectHTML(e){this.domNode?(e&&(this.domNode.innerHTML=e),this.domIsReady=!0):(this.domIsReady=!1,console.error("An error occurred when trying to render this page. DOM node not found."))}prerender(e){this.injectMetaDescription(e.domain),e.bannerAdblockerOnly&&this.hideSalesBanner(),this.injectHTML(e.html)}template(e){var t;this.domIsReady||this.prerender(e),this.injectStyles(e.stylesheet),this.imprint(e.imprint),this.salesBanner(e.salesBanner),e.bannerAdblockerOnly||this.injectJS(e.javascript),null===(t=e.scripts)||void 0===t||t.forEach((e=>{this.injectScript(e)}))}}const Render=new Renderer(APP_TARGET);var Type;!function(e){e[e.Failed=0]="Failed",e[e.Disabled=1]="Disabled",e[e.Redirect=2]="Redirect",e[e.Parking=3]="Parking",e[e.Sales=4]="Sales"}(Type||(Type={}));let State$2=class{get trackingType(){return this._trackingType}set trackingType(e){this._trackingType=e}get track(){return!!this.trackingType}};class Disabled extends State$2{constructor(){super(...arguments),this.type=Type.Disabled}static build(e,t){let n;switch(t===Blocking.BLOCKED&&(n="adblocker"),e.cannotPark){case"disabled_mr":case"disabled_rc":n=e.cannotPark}if(n){const t=new Disabled;return t.reason=n,t.domain=e.domainName,t}}get message(){switch(this.reason){case"adblocker":return"

Content blocked

Please turn off your ad blocker.";case"disabled_mr":return`

Invalid URL

Referral traffic for ${this.domain} does not meet requirements.`;default:return`

No sponsors

${this.domain} currently does not have any sponsors for you.`}}get trackingType(){switch(this.reason){case"adblocker":return"ad_blocked_message";case"disabled_mr":return"invalid_referral";case"disabled_rc":return"revenue_cap_reached";default:return"no_sponsors_message"}}toContext(){return{cannotPark:this.reason}}}class Failed extends State$2{constructor(){super(...arguments),this.type=Type.Failed}static cannotPark({cannotPark:e}){switch(e){case"disabled_b":case"prohibited_ua":case"disabled_fr":case"revenue_cap_reached":case"disabled_mr":case"disabled_rc":case"disabled_cp":case"invalid_domain":{const t=new Failed;return t.reason=e,t}}}static noSponsors({cannotLoadAds:e}){if(e){const e=new Failed;return e.reason="no_sponsors",e}}static fromError(e){const t=new Failed;return t.reason="js_error",t.error=e,t}get track(){return!!this.trackingType}get message(){switch(this.reason){case"disabled_fr":case"disabled_rc":case"no_sponsors":return`\n

No Sponsors

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${this.domain} currently does not have any sponsors for you.

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Invalid URL

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Referral traffic for ${this.domain} does not meet requirements.

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An Error Occurred

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Parking is currently unavailable. We'll be right back.

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Services for this domain name have been disabled.

\n "}}get trackingType(){switch(this.reason){case"disabled_rc":return"revenue_cap_reached";case"disabled_mr":return"invalid_referral";case"adblock":return"ad_blocked_message";case"no_sponsors":return"no_sponsors_message"}}get domain(){return window.location.hostname}toContext(){return{cannotPark:this.reason}}}function unpackPHPArrayObject(e,t){const n=e[t];if(n&&!Array.isArray(n))return n}class Parking extends State$2{constructor(){super(...arguments),this.type=Type.Parking}static build(e,t){const n=new Parking;n.domain=e.domainName,n.html=e.template,n.scripts=e.scripts||[],n.javascript=e.inlineJs,n.stylesheet=e.styles,n.imprint=e.imprintText;const i=unpackPHPArrayObject(e,"salesSettings");n.bannerAdblockerOnly=null==i?void 0:i.banner_adblocker_only;const s=(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status);if(s){const{status:e,location:t,message:s,link:a,type:o}=i;n.salesBanner={message:s,href:a,position:t,theme:o,status:e}}return t.wantsToServeAds?n.trackingType="ctr":s&&window.location.pathname.startsWith("/listing")?n.trackingType="sales":n.trackingType="visit",n}toContext(){return{}}}class Sales extends State$2{constructor(){super(...arguments),this.type=Type.Sales}static build(e){const t=unpackPHPArrayObject(e,"salesSettings");if(!t)return;const{status:n}=t;return["NOT_FOR_SALE","EXTERNAL_MARKET","URL"].includes(n)?void 0:window.location.pathname.startsWith("/listing")?new Sales:void 0}toContext(){return{}}get trackingType(){return"sales"}init(e){window.context=e;const t=document.createElement("script");t.type="text/javascript",t.src=SALES_JS_URL,document.head.append(t)}}class Redirect extends State$2{constructor(){super(...arguments),this.type=Type.Redirect}static build(e,t,n){const i=unpackPHPArrayObject(e,"salesSettings"),{zeroClickDelay:s,skenzoRedirect:a,skenzoUrl:o,showInquiryForm:r,canZeroClick:d,cannotPark:c}=e;if(window.location.pathname.startsWith("/listing")&&["EXTERNAL_MARKET","URL"].includes(null==i?void 0:i.status)){if(null==i?void 0:i.external)return Redirect.toState(i.external,"sales");if(null==i?void 0:i.link)return Redirect.toState(i.link,"sales")}if(n.cannotLoadAds&&n.wantsToServeAds)return Redirect.toState(n.noAdsRedirectUrl,"no_ads_redirect");if(d&&(null==t?void 0:t.reason)){if(null==t?void 0:t.redirect)return Redirect.toState(t.redirect,"zc_redirect",s);if(a&&o)return Redirect.toState(o,"skenzo_redirect")}return(null==i?void 0:i.status)&&"NOT_FOR_SALE"!==(null==i?void 0:i.status)&&!(null==i?void 0:i.banner_adblocker_only)&&(n.cannotLoadAds||n.cannotLoadAds&&!d||r)?Redirect.toState(`${window.location.origin}/listing`):void 0}static toState(e,t,n=0){const i=new Redirect;return i.url=e,i.delay=n,i.trackingType=t,i}toContext(){return{}}}const browserState=()=>{var e,t,n,i,s;const{screen:{width:a,height:o},self:r,top:d,matchMedia:c,opener:l}=window,{documentElement:{clientWidth:h,clientHeight:u}}=document;let p;try{p=(new Date).getTimezoneOffset()/60*-1}catch(e){p=null}return{popup:!(!l||l===window),timezone_offset:p,user_preference:null===(e=null===Intl||void 0===Intl?void 0:Intl.DateTimeFormat())||void 0===e?void 0:e.resolvedOptions(),user_using_darkmode:Boolean(c&&c("(prefers-color-scheme: dark)").matches),user_supports_darkmode:Boolean(c),window_resolution:{width:null!=h?h:0,height:null!=u?u:0},screen_resolution:{width:null!=a?a:0,height:null!=o?o:0},frame:d===r?null:{innerWidth:null!==(t=null==r?void 0:r.innerWidth)&&void 0!==t?t:0,innerHeight:null!==(n=null==r?void 0:r.innerHeight)&&void 0!==n?n:0,outerWidth:null!==(i=null==r?void 0:r.outerWidth)&&void 0!==i?i:0,outerHeight:null!==(s=null==r?void 0:r.outerHeight)&&void 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0:e.pageLoadedCallback,page_method:t.page_method,page_request:t.page_request,page_time:t.page_time,page_url:t.page_url,reportable_channel:t.reportableChannel,reportable_style_id:t.reportableStyleId,tablet:t.tablet,template_id:t.templateId,type:n,user_has_ad_blocker:t.user_has_ad_blocker,user_id:t.userId,uuid:t.uuid,zeroclick:t.zeroClick},browserState())},trackVisit=({callbacks:e,context:t},n,i="")=>{const s=`${i}/${TRACKING_URL}`,a=i?"include":"same-origin",o=buildSignature({callbacks:e,context:t},n);let r={};"click"===n&&(r={[ClickKey]:"true",[SessionKey]:t.uuid,[NoCacheKey]:Date.now().toString()}),fetch(s,{method:"POST",headers:{Accept:"application/json","Content-Type":"application/json"},credentials:a,body:JSON.stringify(Object.assign({signature:encode(o)},r))})};var State$1;!function(){if(!window.CustomEvent){function e(e,t){t=t||{bubbles:!1,cancelable:!1,detail:void 0};const n=document.createEvent("CustomEvent");return n.initCustomEvent(e,t.bubbles,t.cancelable,t.detail),n}e.prototype=window.Event.prototype,window.CustomEvent=e}}(),function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failed=2]="Failed"}(State$1||(State$1={}));class Provider{get providerCtor(){return this.constructor}constructor(e){this.state=new Map,this.injectedAt=new Map,this.timeoutAt=new Map,this.timeoutSeconds=5,this.handlePixelEvent=e=>{this.keys.forEach((t=>{switch(this.state.get(t)){case State$1.Failed:break;case State$1.Pending:setTimeout((()=>this.handlePixelEvent(e)),100);break;case State$1.Loaded:this.onPixelEvent(e,t)}}))},this.watch=e=>{switch(this.state.get(e)){case State$1.Loaded:case State$1.Failed:break;case State$1.Pending:this.isLoaded(e)?this.state.set(e,State$1.Loaded):this.isTimedOut(e)?this.state.set(e,State$1.Failed):setTimeout((()=>this.watch(e)),50)}},this.config=e,this.keys.length>0?this.keys.forEach((e=>{this.state.set(e,State$1.Pending);const t=new Date;t.setSeconds(t.getSeconds()+this.timeoutAfter()),this.timeoutAt.set(e,t),this.injectPixel(e)})):this.state.set("",State$1.Failed)}get keys(){return this.config?Object.keys(this.config):[]}getPixelEvents(e){var t,n;return null===(n=null===(t=this.config)||void 0===t?void 0:t[e])||void 0===n?void 0:n.pixel_events}injectPixel(e){this.injectedAt.has(e)||(this.injectedAt.set(e,new Date),this.inject(e),this.watch(e))}inject(e){if(!this.providerCtor.scriptInjected){const e=document.createElement("script");e.text=this.getScript(),document.head.appendChild(e),this.providerCtor.scriptInjected=!0}this.init(e)}isTimedOut(e){return+new Date>=+(this.timeoutAt.get(e)||0)}timeoutAfter(){return this.timeoutSeconds}selectPixelEvents(e,t){const n=this.getPixelEvents(t);if(Array.isArray(n))return n.filter((t=>"term-view"===t.trigger&&"visit"===e||(!(!["term-click","ad-view"].includes(t.trigger)||"ctr"!==e)||"ad-click"===t.trigger&&"click"===e)))}}class Facebook extends Provider{getScript(){return"!function(f,b,e,v,n,t,s){if(f.fbq)return;n=f.fbq=function(){n.callMethod?n.callMethod.apply(n,arguments):n.queue.push(arguments)};if(!f._fbq)f._fbq=n;n.push=n;n.loaded=!0;n.version='2.0';n.queue=[];t=b.createElement(e);t.async=!0;t.src=v;s=b.getElementsByTagName(e)[0];s.parentNode.insertBefore(t,s)}(window, document,'script','https://connect.facebook.net/en_US/fbevents.js');"}init(e){window.fbq&&window.fbq("init",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&(e.custom?window.fbq("trackSingleCustom",t,e.event):window.fbq("trackSingle",t,e.event))}))}isLoaded(e){return!!window.fbq&&window.fbq.getState&&window.fbq.getState(e)}}Facebook.scriptInjected=!1;class Outbrain extends Provider{getScript(){return`!function(_window, _document) { var OB_ADV_ID = ${JSON.stringify(this.keys)}; if (_window.obApi) { var toArray = function(object) { return Object.prototype.toString.call(object) === '[object Array]' ? object : [object]; }; _window.obApi.marketerId = toArray(_window.obApi.marketerId).concat(toArray(OB_ADV_ID)); return; } var api = _window.obApi = function() { api.dispatch ? api.dispatch.apply(api, arguments) : api.queue.push(arguments); }; api.version = '1.1'; api.loaded = true; api.marketerId = OB_ADV_ID; api.queue = []; var tag = _document.createElement('script'); tag.async = true; tag.src = '//amplify.outbrain.com/cp/obtp.js'; tag.type = 'text/javascript'; var script = _document.getElementsByTagName('script')[0]; script.parentNode.insertBefore(tag, script); }(window, document);`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.obApi("track",e.event)}))}isLoaded(e){return!!window.obApi}}Outbrain.scriptInjected=!1;class Revcontent extends Provider{getScript(){return"var script=document.createElement('script');script.src='https://assets.revcontent.com/master/rev.js';document.head.appendChild(script);"}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.rev("event",e.event)}))}isLoaded(e){return!!window.rev}}Revcontent.scriptInjected=!1;class Taboola extends Provider{getScript(){return`window._tfa = window._tfa || [];!function (t, f, a, x) {if (!document.getElementById(x)) {t.async = 1;t.src = a;t.id=x;f.parentNode.insertBefore(t, f);}}(document.createElement('script'),document.getElementsByTagName('script')[0],'//cdn.taboola.com/libtrc/unip/${this.keys[0]}/tfa.js','tb_tfa_script');`}init(e){}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{if(e){const n=parseInt(t,10);window._tfa.push({notify:"event",name:e.event,id:n})}}))}isLoaded(e){return Array.isArray(window._tfa)}}Taboola.scriptInjected=!1;class Tiktok extends Provider{getScript(){return'!function (w, d, t) {w.TiktokAnalyticsObject=t;var ttq=w[t]=w[t]||[];ttq.methods=["page","track","identify","instances","debug","on","off","once","ready","alias","group","enableCookie","disableCookie"],ttq.setAndDefer=function(t,e){t[e]=function(){t.push([e].concat(Array.prototype.slice.call(arguments,0)))}};for(var i=0;i{e&&window.ttq.instance(t).track(e.event)}))}isLoaded(){return!!window.ttq}}Tiktok.scriptInjected=!1;class GoogleAds extends Provider{getScript(){return`var s=document.createElement('script');s.async=1;s.src='https://www.googletagmanager.com/gtag/js?id=${this.keys[0]}';document.head.appendChild(s);window.dataLayer=window.dataLayer||[];function gtag(){dataLayer.push(arguments)}gtag('set','allow_ad_personalization_signals',false);gtag('js',new Date);`}init(e){window.gtag&&window.gtag("config",e)}onPixelEvent(e,t){const n=this.selectPixelEvents(e,t);n&&n.forEach((e=>{e&&window.gtag("event","conversion",{send_to:`${t}/${e.event}`})}))}isLoaded(e){return!!window.gtag}}GoogleAds.scriptInjected=!1;const ADS_PARAM$1=CAFKey,MESSAGE_PREFIX="FSXDC,.aCS:",ALLOWED_ORIGINS=["https://www.google.com","https://www.adsensecustomsearchads.com","https://syndicatedsearch.goog","https://googleadservices.com"];class Pixels{static build(e){const t=unpackPHPArrayObject(e,"pixel_tracking_data");if(t)return t.useAltTikTokEventsForAdsPlatformUser=e.is_ads,new Pixels(t)}constructor(e){this.onPixelEvent=e=>{const{detail:{type:t}}=e;switch(t){case"visit":case"ctr":case"click":this.providers.forEach((e=>e.handlePixelEvent(t)))}},this.providers=[],e.facebook&&Object.keys(e.facebook).forEach((t=>{this.providers.push(new Facebook({[t]:e.facebook[t]}))})),e.tiktok&&Object.keys(e.tiktok).forEach((t=>{this.providers.push(new Tiktok({[t]:e.tiktok[t]}))})),e.taboola&&Object.keys(e.taboola).forEach((t=>{this.providers.push(new Taboola({[t]:e.taboola[t]}))})),e.revcontent&&Object.keys(e.revcontent).forEach((t=>{this.providers.push(new Revcontent({[t]:e.revcontent[t]}))})),e.outbrain&&this.providers.push(new Outbrain(e.outbrain)),e.googleads&&Object.keys(e.googleads).forEach((t=>{this.providers.push(new GoogleAds({[t]:e.googleads[t]}))}))}listenForEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}));window.onmessage=e=>{const{origin:t,data:n}=e;ALLOWED_ORIGINS.includes(t)&&"string"==typeof n&&(null==n?void 0:n.startsWith(MESSAGE_PREFIX))&&new URLSearchParams(window.location.search).has(ADS_PARAM$1)&&document.dispatchEvent(new CustomEvent("pixel",{detail:{type:"click"}}))}}listenForPixelEvents(){document.addEventListener("pixel",(e=>{this.onPixelEvent(e)}))}dispatchEvent(e){document.dispatchEvent(new CustomEvent("pixel",{detail:e}))}}var State;!function(e){e[e.Pending=0]="Pending",e[e.Loaded=1]="Loaded",e[e.Failure=2]="Failure",e[e.TimedOut=3]="TimedOut",e[e.Errored=4]="Errored"}(State||(State={}));const CAF_SCRIPT_SRC=`https://www.google.com/adsense/domains/caf.js?${GOOGLE_MV3_URL_PARAMS}`,TIMEOUT_SCRIPTS=Number(GOOGLE_CAF_TIMEOUT_SCRIPTS),TIMEOUT_CALLBACKS=Number(GOOGLE_CAF_TIMEOUT_CALLBACKS);class StateMachine{constructor(){this.state=State.Pending}transitionTo(e){this.state=e}transitionFromPendingTo(e){this.done||(this.state=e)}get loaded(){return this.state===State.Loaded}get timedOut(){return this.state===State.TimedOut}get done(){return this.state!==State.Pending}}class Ads{constructor(e,t){this.state={script:new StateMachine,blocks:new StateMachine},this.blocksLoaded=[],this.injectScriptTags=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.type="text/javascript",t.src=CAF_SCRIPT_SRC,t.addEventListener("load",(()=>e(!0))),t.addEventListener("error",(()=>e(!1))),document.body.appendChild(t),TIMEOUT_SCRIPTS>0&&setTimeout((()=>e(!1)),TIMEOUT_SCRIPTS)}))})),this.onPageLoaded=(e,t)=>{if(this.pageLoaded={requestAccepted:e,status:t},this.state.script.done)return;const n=null==t?void 0:t.error_code;n?(this.state.script.transitionTo(State.Failure),this.failureReason=`caf_pageloaderror_${n}`):this.state.script.transitionTo(State.Loaded)},this.onBlockLoaded=(e,t,n,i)=>{this.blocksLoaded.push({containerName:e,adsLoaded:t,isExperimentVariant:n,callbackOptions:i}),this.state.blocks.done||(t?this.state.blocks.transitionTo(State.Loaded):this.blocksLoaded.length>=this.blocks.length&&(this.state.blocks.transitionTo(State.Failure),this.failureReason=`caf_adloadfail_${e}`))},this.onTimeout=()=>{this.state.script.transitionFromPendingTo(State.TimedOut),this.state.blocks.transitionFromPendingTo(State.TimedOut)},this.blocks=e,this.options=t}get loaded(){return this.state.script.loaded&&!this.blocksLoaded.map((e=>e.adsLoaded)).includes(!1)}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=()=>{const n=performance.now();if(this.state.blocks.done)return this.cafLoadTime=Math.round(n-this.cafStartTime),void e();const i=this.blocksLoaded.map((e=>e.adsLoaded));i.includes(!1)||i.length>=this.blocks.length?e():setTimeout(t,50)};t()}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){try{const e=yield this.injectScriptTags();return this.cafStartTime=performance.now(),e&&void 0!==window.google?(new window.google.ads.domains.Caf(Object.assign(Object.assign({},this.options),{pageLoadedCallback:this.onPageLoaded,adLoadedCallback:this.onBlockLoaded}),...this.blocks),TIMEOUT_CALLBACKS>0&&setTimeout(this.onTimeout,TIMEOUT_CALLBACKS),yield new Promise((e=>{const t=()=>{this.state.script.done?e():setTimeout(t,10)};t()}))):void this.state.script.transitionTo(State.Failure)}catch(e){return void(this.error=e.toString())}}))}toCallbacks(){return{adLoadedCallback:this.blocksLoaded.slice(-1)[0],pageLoadedCallback:this.pageLoaded,cafTimedOut:this.state.script.timedOut||this.state.blocks.timedOut,cafLoadedMs:this.cafLoadTime,googleAdsFailure:!!this.failureReason}}toContext(){const e={cafScriptWasLoaded:this.state.script.loaded,cafScriptLoadTime:this.cafLoadTime,callbacks:this.toCallbacks};return this.error&&(e.js_error={message:this.error}),this.state.script.loaded||(e.zeroclick={reason:"googleAdsFailure"}),e}mockFailedState(){this.state.blocks.transitionTo(State.Failure),this.state.script.transitionTo(State.Failure)}}class TagManager{constructor(e){this.injected=!1,this.identifier=e}inject(){if(this.injected)return;if(!this.identifier)return;if("TEST"===this.identifier)return;const e=document.createElement("script");e.setAttribute("src",`https://www.googletagmanager.com/gtag/js?id=${this.identifier}`),document.head.appendChild(e),this.track(),this.injected=!0}track(){this.push("js",new Date),this.push("config",this.identifier)}push(e,t){window.dataLayer||(window.dataLayer=[]),window.dataLayer.push(arguments)}}const ADS_PARAM=CAFKey,ADS_TRACKING_URL="_tr",BLOCKS_TYPE="ads",BLOCKS_CONTAINER="rs",KNOWN_CAF_PARAMS=["caf","query","afdToken","pcsa","nb","nm","nx","ny","is","clkt"];class Google{static build({pageOptions:e,preferredLanguage:t,blocks:n,googleAnalytics:i},s,a,o){let r={};e&&(r=Object.assign({},e),r.hl||(r.hl=t));let d=null==e?void 0:e.resultsPageBaseUrl;d||(d=window.location.origin);return new Google(s.uuid,n,r,i,d,o)}constructor(e,t,n,i,s,a){this._blocks=t,this._pageOptions=n,this.uuid=e,this._baseURL=new URL(s),this._signature=a,this.ads=new Ads(this.blocks,this.pageOptions),this.tagManager=new TagManager(i)}injectTagManager(){this.tagManager.inject()}injectAds(){return __awaiter(this,void 0,void 0,(function*(){yield this.ads.inject()}))}waitForBlocks(){return __awaiter(this,void 0,void 0,(function*(){return this.ads.waitForBlocks()}))}get blocks(){return(this._blocks||[]).filter((e=>this.wantsToServeAds?e.type===BLOCKS_TYPE:e.container===BLOCKS_CONTAINER)).map((e=>{const t=this.baseURL;new URLSearchParams(window.location.search).forEach(((e,n)=>{t.searchParams.has(n)||t.searchParams.append(n,e)}));const n=Object.assign({},e);if(n.resultsPageBaseUrl=t.toString(),this.wantsToServeAds){const e=new URLSearchParams;e.append("click","true"),e.append("session",this.uuid);const t=Object.assign({},this._signature);delete t.ad_loaded_callback,delete t.caf_loaded_ms,delete t.caf_timed_out,delete t.flex_rule,delete t.frame,delete t.js_error,delete t.no_ads_redirect,delete t.page_headers,delete t.page_request,delete t.page_loaded_callback,delete t.popup,delete t.screen_resolution,delete t.user_has_ad_blocker,delete t.user_preference,delete t.user_supports_darkmode,delete t.user_using_darkmode,delete t.zeroclick,e.append("signature",encode(t)),n.clicktrackUrl=`${TRACKING_DOMAIN}${ADS_TRACKING_URL}?${e.toString()}`}return n}))}get baseURL(){const e=new URL(this._baseURL.origin);return e.searchParams.append(ADS_PARAM,"1"),this._baseURL.searchParams.forEach(((t,n)=>{e.searchParams.append(n,t)})),e}get pageOptions(){const e=Object.assign({},this._pageOptions);return Object.keys(this._pageOptions).forEach((t=>{t.startsWith("bodis")&&delete e[t]})),e}get cannotLoadAds(){return!this.ads.loaded}get wantsToServeAds(){return new URLSearchParams(window.location.search).has(ADS_PARAM)}get adsMode(){return this.ads.loaded&&this.wantsToServeAds}get adsReady(){return this.wantsToServeAds&&!this.cannotLoadAds}get noAdsRedirectUrl(){const e=new URLSearchParams(window.location.search);return KNOWN_CAF_PARAMS.forEach((t=>e.delete(t))),`${window.location.origin}?${e.toString()}`}get callbacks(){return this.ads.toCallbacks()}toContext(){return Object.assign({blocks:this.blocks,pageOptions:this.pageOptions},this.ads.toContext())}}class CookieConsentManager{constructor(){this.injectScriptTag=()=>__awaiter(this,void 0,void 0,(function*(){return new Promise((e=>{const t=document.createElement("script");t.setAttribute("src",COOKIE_CONSENT_JS_URL),t.addEventListener("load",(()=>this.awaitConsent(e))),t.addEventListener("error",(()=>e(!1))),document.head.appendChild(t)}))}))}inject(){return __awaiter(this,void 0,void 0,(function*(){this.injected||!COOKIE_CONSENT_JS_URL||isLocal()||(this.injected=yield this.injectScriptTag())}))}awaitConsent(e){let t=0;const n=setInterval((()=>{t+=1,20===t&&(clearInterval(n),e(!0)),void 0!==window.__tcfapi&&(window.addEventListener("ConsentActivity",(t=>{const{detail:{status:n}}=t;n&&e(!0)})),clearInterval(n))}),50)}}class Cheq{constructor(e){let t;if(t="string"==typeof e?parseInt(e,10):e,t<0||t>100)throw new Error("Load percentage must be between 0 and 100");this.loadPercentage=t}inject(e,t,n){return __awaiter(this,void 0,void 0,(function*(){if(!n||this.injected)return;100*Math.random()<=this.loadPercentage&&(this.injected=this.injectScriptTag(e,t))}))}injectScriptTag(e,t){const n=document.createElement("script");return n.type="text/javascript",n.async=!0,n.setAttribute("src","https://ob.forseasky.com/i/148870ae21863d775c347e8893c985af.js"),n.setAttribute("data-ch","cheq4ppc"),n.setAttribute("data-uvid",e),n.setAttribute("data-utm-campaign",t.toString()),n.className="ct_clicktrue_73521",document.head.appendChild(n),!0}}class App{main(){var e,t;return __awaiter(this,void 0,void 0,(function*(){if(this.parkResponse=decode(),this.findDomainResponse=yield getFindDomain(),!this.findDomainResponse)throw new Error("Domain failed to load.");this.pixels=Pixels.build(this.findDomainResponse),null===(e=this.pixels)||void 0===e||e.listenForEvents(),this.adblock=new Adblock,yield this.adblock.inject(),this.google=Google.build(this.findDomainResponse,this.parkResponse,this.adblock,buildSignature({context:this.context,callbacks:null===(t=this.google)||void 0===t?void 0:t.callbacks},"click")),this.google.injectTagManager();const n=Parking.build(this.findDomainResponse,this.google);Render.prerender(n),this.cheq=new Cheq(AFD_CHEQ_LOAD_PERCENTAGE),this.cheq.inject(this.parkResponse.uuid,this.findDomainResponse.userId,this.findDomainResponse.referral),this.cookieConsentManager=new CookieConsentManager,yield this.cookieConsentManager.inject();let i=Failed.cannotPark(this.findDomainResponse);if(i)return void(yield this.transitionToFailed(i,n));yield this.google.injectAds();let s=Disabled.build(this.findDomainResponse,this.adblock.state);if(s)return void(yield this.transitionToDisabled(s,n));const a=this.adblock.hasAdblocker();a&&this.adblock.handleAdblocked();const o=Sales.build(this.findDomainResponse);if(o)return void(yield this.transitionToSales(o));this.eligibleForZeroClick&&(this.zeroClickResponse=yield getZeroClick(this.context));const r=Redirect.build(this.findDomainResponse,this.zeroClickResponse,this.google);if(r)yield this.transitionToRedirect(r);else{if(a)return s=Disabled.build(this.findDomainResponse,this.adblock.state),void(yield this.transitionToDisabled(s,n));i=Failed.noSponsors(this.google),i?yield this.transitionToFailed(i,n):yield this.transitionToParking(n)}}))}transitionToParking(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.template(e),Render.revealPage(),yield this.google.waitForBlocks(),yield this.track()}))}transitionToRedirect(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e;const t=this.track();Render.revealPage(),yield waiter(e.delay,(e=>Render.loading(e))),yield t,window.location.href=e.url,log(`➡ Redirecting [${e.url}]`)}))}transitionToFailed(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),Render.revealPage(),yield this.track()}))}transitionToSales(e){return __awaiter(this,void 0,void 0,(function*(){this.state=e,e.init(this.context),yield this.track()}))}transitionToDisabled(e,t){return __awaiter(this,void 0,void 0,(function*(){this.state=e,Render.message(e.message),Render.injectJS(t.javascript),"adblocker"===e.reason&&t.bannerAdblockerOnly&&Render.revealSalesBanner(),Render.revealPage(),yield this.track()}))}track(){var e;return __awaiter(this,void 0,void 0,(function*(){if(!this.state.track)return Promise.resolve();try{const t=this.state.trackingType;return null===(e=this.pixels)||void 0===e||e.dispatchEvent({type:t}),trackVisit({context:this.context,callbacks:this.google.callbacks},t)}catch(e){return}}))}get eligibleForZeroClick(){const{cannotPark:e,canZeroClick:t,zeroClick:n}=this.findDomainResponse,{cannotLoadAds:i,wantsToServeAds:s}=this.google;return this.adblock.state!==Blocking.BLOCKED&&(!!t&&(!!e||(!(!i||s)||!!(null==n?void 0:n.reason))))}get context(){var e,t,n,i;const s=this.findDomainResponse,a=this.parkResponse,o=null===(e=this.state)||void 0===e?void 0:e.toContext(),r=null===(t=this.adblock)||void 0===t?void 0:t.toContext(),d=null===(n=this.google)||void 0===n?void 0:n.toContext(),c=browserState(),l=Object.assign(Object.assign({},null===(i=this.findDomainResponse)||void 0===i?void 0:i.zeroClick),this.zeroClickResponse);return Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign(Object.assign({app_version:APP_VERSION},s),a),r),d),o),c),{zeroClick:l})}init(){return __awaiter(this,void 0,void 0,(function*(){try{window.__parkour=this,yield this.main()}catch(e){console.error("app",e);const t=Failed.fromError(e);this.state=t,Render.message(t.message),Render.revealPage()}}))}}(new App).init(),exports.App=App}));
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