FrancophonIA/ELRC3.0 huggingface dataset:
English: However, your doctor may decide that it is right for you to learn how to inject Silapo under the skin (subcutaneously) yourself.
Slovenian: Lahko pa se bo zdravnik odločil, da se lahko naučite, kako si zdravilo Silapo pod kožo (subkutano) injicirate sami.
English: The four carbohydrate chains are attached via three N-glycosidic bonds and one O-glycosidic bond to the protein.
Slovenian: Štiri ogljikovodikove verige so s tremi N-glikozidnimi vezmi in eno O-glikozidno vezjo pritrjene na protein.
English: Treatment should only be given to patients with moderate anaemia (no iron deficiency), if blood saving procedures are not available or insufficient when the scheduled major elective surgery requires a large volume of blood (4 or more units of blood for females or 5 or more units for males).
Slovenian: Tovrstno zdravljenje smemo predpisati samo bolnikom z zmerno anemijo (hemoglobin (brez pomanjkanja železa), kadar postopki za zmanjšanje izgube krvi niso na razpolago ali če ne zadoščajo za načrtovani večji kirurški poseg, pri katerem je potrebna večja količina krvi (4 ali več enot krvi za ženske oz. 5 ali več enot za moške).
English: Adult patients on peritoneal dialysis
Slovenian: Odrasli bolniki na peritonealni dializi
English: Erythroid response was defined according to International Working Group (IWG) 2006 criteria as a haemoglobin increase ≥1.5 g/dl from baseline or a reduction of RBC units transfused by an absolute number of at least 4 units every 8 weeks compared to the 8 weeks prior to baseline, and a response duration of at least 8 weeks.
Slovenian: Eritroidni odziv so opredelili po merilih Mednarodne delovne skupine (IWG - International Working Group) iz leta 2006 kot zvišanje ravni hemoglobina za ≥ 1,5 g/dl od izhodišča ali zmanjšanje absolutnega števila enot koncentriranih eritrocitov, prejetih s transfuzijo, za vsaj 4 enote vsakih 8 tednov v primerjavi z 8 tedni pred izhodiščem in trajanje odziva vsaj 8 tednov.
English: Consequently, erythropoietin should generally be used during pregnancy and lactation only if the potential benefit outweighs the potential risk to the foetus.
Slovenian: Zato se med nosečnostjo in dojenjem eritropoetin v splošnem sme uporabljati le, če možne koristi odtehtajo možna tveganja za plod.
English: The extent to which these outcomes might apply to the administration of recombinant human erythropoietin to patients with cancer, treated with chemotherapy to achieve haemoglobin concentrations less than 13 g/dl, is unclear because few patients with these characteristics were included in the data reviewed.
Slovenian: Obseg, v katerem ti izidi veljajo tudi za dajanje rekombinantnega humanega eritropoetina bolnikom z rakom, ki sočasno prejemajo tudi kemoterapijo, z namenom doseganja koncentracije hemoglobina pod 13 g/dl, ni znan, ker je bilo v podatke za ocenjevanje vključenih premalo takih bolnikov.
English: The most frequent adverse reaction during treatment with epoetin alfa is a dose-dependent increase in blood pressure or aggravation of existing hypertension.
Slovenian: Najpogostejši neželeni učinek, ki se pojavi med zdravljenjem z epoetinom alfa, je od odmerka odvisno zvišanje krvnega tlaka ali poslabšanje obstoječe hipertenzije.
English: The percentage of subjects who were transfused in the epoetin alfa group decreased from 51.8% in the 8 weeks prior to baseline to 24.7% between weeks 16 and 24, compared to the placebo group which had an increase in transfusion rate from 48.9% to 54.1% over the same time periods.
Slovenian: Odstotek preskušancev, ki so prejeli transfuzijo, iz skupine, ki je prejemala epoetin alfa, se je zmanjšal z 51,8 % pri 8 tednih pred izhodiščem na 24,7 % v času med 16. in 24. tednom v primerjavi s skupino, ki je prejemala placebo, pri kateri se je stopnja transfuzije v istem obdobju povečala z 48,9 % na 54,1 %.
English: After administration of erythropoietin, the number of erythrocytes, the Hb values and reticulocyte counts increase as well as the
Slovenian: Po injiciranju eritropoetina se dvigne tako število eritrocitov, vrednosti Hb in število retikulocitov, kot tudi hitrost vgrajevanja
English: Use should be restricted to patients with moderate anaemia (e.g. haemoglobin concentration range between 10 to 13 g/dl) who do not have an autologous predonation programme available and with expected moderate blood loss (900 to 1 800 ml).
Slovenian: Uporabo je treba omejiti na bolnike z zmerno anemijo (npr. razpon koncentracije hemoglobina od 10 do 13 g/dl), ki jim program avtolognega darovanja krvi ni na voljo in pri katerih se pričakuje zmerna izguba krvi (od 900 do 1 800 ml).
English: Handling instructions for Silapo:
Slovenian: Navodila za rokovanje z zdravilom Silapo:
English: If possible, iron supplementation should be initiated prior to starting epoetin zeta therapy to achieve adequate iron stores.
Slovenian: Če je mogoče, je treba z nadomeščanjem železa začeti pred zdravljenjem z epoetinom zeta, da se dosežejo ustrezne zaloge železa.
English: In 2 studies with extended interval dosing of erythropoietin (3 times per week, once weekly, once every 2 weeks and once every 4 weeks) some patients with longer dosing intervals did not maintain adequate haemoglobin levels and reached protocol-defined haemoglobin withdrawal criteria (0% in once weekly, 3.7% in once-every-2-weeks and 3.3% in the once-every-4-weeks groups).
Slovenian: V dveh študijah s podaljšanim odmernim intervalom eritropoetina (trikrat tedensko, enkrat tedensko, enkrat na dva tedna in enkrat na štiri tedne) nekateri bolniki s podaljšanim odmernim intervalom niso ohranili ustreznih nivojev hemoglobina in so dosegli v protokolu podane izključitvene kriterije (0 % v skupini z enkrat tedenskim odmerjanjem, 3,7 % pri odmerjanju enkrat na dva tedna in 3,3 % pri odmerjanju enkrat na 4 tedne).
English: These studies have shown a consistent unexplained statistically significant excess mortality in patients who have anaemia associated with various common cancers who received recombinant human erythropoietin compared to controls.
Slovenian: Te študije so pokazale dosledno nepojasnjen statistično pomemben presežek smrtnosti pri bolnikih, katerih anemija je povezana z različnimi običajnimi vrstami raka in ki so za razliko od kontrol prejeli rekombinantni humani eritropoetin.
English: Some patients with more extended dosing intervals (greater than once weekly) of epoetin may not maintain adequate haemoglobin levels (see section 5.1) and may require an increase in epoetin dose.
Slovenian: Nekateri bolniki z daljšimi odmernimi intervali epoetina (daljšimi kot enkrat tedensko) morda ne bodo ohranili ustreznih nivojev hemoglobina (glejte poglavje 5.1) in bodo morda potrebovali višji odmerek epoetina.
English: If PRCA is diagnosed, therapy with Silapo must be immediately discontinued and testing for erythropoietin antibodies should be considered.
Slovenian: Če pride do diagnoze PRCA, je treba zdravljenje z zdravilom Silapo takoj prekiniti in razmisliti o testiranju na protitelesa za eritropoetin.
English: • Swelling of the ankles, feet or fingers
Slovenian: • Otekanje gležnjev, stopal ali prstov.
English: The pre-filled syringes contain between 0.3 and 1 ml solution, depending on the content of epoetin zeta (see “What Silapo contains”).
Slovenian: Vnaprej napolnjene brizge vsebujejo med 0,3 in 1 ml raztopine, odvisno od vsebnosti epoetin zeta (glejte "Kaj vsebuje zdravilo Silapo").
English: Patients should be monitored closely to ensure that the lowest approved dose of Silapo is used to provide adequate control of the symptoms of anaemia.
Slovenian: Bolnike morate pozorno nadzorovati, da bi zagotovili uporabo najnižjega odobrenega odmerka zdravila Silapo za primeren nadzor simptomov anemije.
English: Based on the results from clinical trials with other authorised erythropoietins approximately 8% of patients treated with erythropoietin are expected to experience adverse reactions.
Slovenian: Na osnovi kliničnih preskušanj z drugimi eritropoetini z dovoljenjem za prometje pričakovati, da bo do neželenih učinkov prišlo pri približno 8% bolnikov, ki se jih zdravi z eritropoetinom.
English: The studies either recruited patients who were being treated with chemotherapy (two studies) or used patient populations in which erythropoiesis stimulating agents are not indicated: anaemia in patients with cancer not receiving chemotherapy, and head and neck cancer patients receiving radiotherapy.
Slovenian: V študije so vključili bolnike, ki so bili deležni kemoterapije (dve študiji) ali pa so uporabljali populacije bolnikov, pri katerih zdravila za stimulacijo eritropoeze niso bila indicirana: anemija pri bolnikih z rakom, ki ne prejemajo kemoterapije ter bolniki z rakom glave in vratu, ki prejemajo terapijo z obsevanjem.
English: Treatment with Silapo has to be initiated under the supervision of physicians experienced in the management of patients with above indications.
Slovenian: Zdravljenje z zdravilom Silapo je treba začeti pod nadzorom zdravnika, ki ima izkušnje z zdravljenjem bolnikov z zgoraj navedenimi indikacijami.
English: • Severe allergic reaction that may include: o a swollen face, lips, mouth, tongue or throat o difficulty swallowing or breathing o itchy rash (hives)
Slovenian: • Hude alergijske reakcije, ki lahko vključujejo: o otekanje obraza, ustnic, ust, jezika ali žrela, o težave pri požiranju ali dihanju, o srbeč izpuščaj (koprivnica).
English: If blood pressure cannot be well controlled, Silapo treatment should be discontinued.
Slovenian: Če krvnega tlaka ni mogoče obvladati, je treba zdravljenje z zdravilom Silapo prekiniti.
English: PRCA may be caused by the production of antibodies against the erythropoietin product and, in the following, to your own erythropoietin.
Slovenian: Do PRCA lahko pride zaradi tvorjenja protiteles proti eritropoetinu v zdravilu in posledično proti Vašemu lastnemu eritropoetinu.
English: Maintenance phase: During the maintenance phase, Silapo can be administered either 3 times per week, and in the case of subcutaneous administration, once weekly or once every 2 weeks.
Slovenian: Vzdrževalna faza: Med vzdrževalno fazo se zdravilo Silapo lahko daje bodisi trikrat tedensko in v primeru subkutanega dajanja enkrat tedensko ali enkrat na vsaka dva tedna.
English: All other causes of anaemia (iron deficiency, haemolysis, blood loss, vitamin B12- or folate deficiencies) should be considered and treated prior to initiating and during therapy with Silapo.
Slovenian: Vse druge vzroke anemije (pomanjkanje železa, hemoliza, izguba krvi, pomanjkanje folne kisline ali vitamina B12) je treba izključiti oziroma zdraviti pred začetkom zdravljenja in med zdravljenjem z zdravilom Silapo.
English: Median time from baseline to first transfusion was statistically significantly longer in the epoetin alfa group compared to placebo (49 vs. 37 days; p=0.046).
Slovenian: Mediani čas od izhodišča do prve transfuzije je bil statistično značilno daljši v skupini, ki je prejemala epoetin alfa, v primerjavi s skupino, ki je prejemala placebo (49 dni v primerjavi s 37 dnevi; p = 0,046).
English: After 4 weeks of treatment the time to first transfusion was further increased in the epoetin alfa group (142 vs. 50 days, p=0.007).
Slovenian: Po 4 tednih zdravljenja se je čas do prve transfuzije v skupini, ki je prejemala epoetin alfa, še dodatno podaljšal (142 dni v primerjavi s 50 dnevi; p = 0,007).
English: • you are at risk of blood clots in the veins (deep venous thrombosis) - for example, if you have had clots before.
Slovenian: • če pri vas obstaja tveganje za nastanek krvnih strdkov v venah (globoka venska tromboza) - na primer, če ste imeli krvne strdke že v preteklosti.
English: Use in children and adolescents up to 18 years receiving haemodialysis In children the doctor will maintain the haemoglobin concentration between 9.5 and 11 g/dl
Slovenian: Uporaba pri otrocih in mladostnikih do 18 leta na hemodializi Zdravnik bo koncentracijo hemoglobina pri otrocih vzdrževal med 9,5 in 11 g/dl.
English: • The recommended dose is 600 IU per kilogram bodyweight once a week.
Slovenian: • Priporočeni odmerek je 600 i.e.na kilogram telesne mase enkrat na teden.
English: Your doctor will order blood tests, and may adjust the dose, depending on how your anaemia responds to Silapo treatment.
Slovenian: Vaš zdravnik bo naročil krvne preiskave in morda prilagodil odmerek, odvisno od tega, kako se anemija odziva na zdravljenje z zdravilom Silapo.
English: • have recently had a heart attack or stroke
Slovenian: • ste pred kratkim imeli srčno ali možgansko kap,
English: - Occlusion in the connection between artery and vein (shunt thrombosis) may occur especially if you have low blood pressure or if your arteriovenous fistula has complications.
Slovenian: - Možna je obstrukcija spoja med arterijo in veno (tromboza šanta), še posebej, če imate nizek krvni tlak ali se na vaši arteriovenski fistuli kažejo zapleti.
English: • Silapo is given by injection under the skin each week for three weeks before surgery and on the day of surgery.
Slovenian: • Zdravilo Silapo se injicira pod kožo vsak teden tri tedne pred kirurškim posegom in na dan kirurškega posega.
English: • Cerebral haemorrhages.
Slovenian: • Krvavitve v možganih.
English: In haemodialysed patients, a bolus injection may be given during the dialysis session through a suitable venous port in the dialysis line.
Slovenian: Bolnikom na hemodializi lahko med dializo injicirate bolus skozi ustrezni venski dostop na dializni liniji.
English: • Flu-like symptoms, such as headache, aches and pains in the joints, feeling of weakness, chills, tiredness and dizziness.
Slovenian: • Gripi podobni simptomi, kot so glavobol, bolečine v sklepih, občutek šibkosti, mrzlica, utrujenost in omotica.
English: As with other haematopoietic growth factors, erythropoietin has shown in vitro stimulating properties on human endothelial cells.
Slovenian: Kot pri drugih hematopoetskih rastnih faktorjih je eritropoetin in vitro imel stimulativne učinke na celice človeškega endotelija.
English: Blood pressure should be closely monitored and adequately controlled in all epoetin treatment naïve as well as pre-treated patients before, at initiation of, and during treatment with Silapo.
Slovenian: Krvni tlak je treba skrbno preverjati in ustrezno nadzorovati pri vseh bolnikih, ki še niso bili zdravljeni z epoetinom, ter tudi pri bolnikih, ki so z njim že bili zdravljeni, ob začetku in med zdravljenjem z zdravilom Silapo.
English: These reports are based on in vitro findings from human tumour samples, but are of uncertain significance in the clinical situation.
Slovenian: Ta poročila slonijo na in vitro rezultatih vzorcev človeških tumorjev, njih klinična pomembnost pa ni gotova.
English: Patients should not be switched to another medicinal product as anti-erythropoietin antibodies cross-react with other erythropoietins.
Slovenian: Bolnikom se ne sme začeti dajati kakšno drugo zdravilo, ker eritropoetinska protitelesa navzkrižno reagirajo z drugimi eritropoetini.
English: Patients were stratified according to their baseline haemoglobin (≤ 10 g/dl, > 10 to ≤ 13 g/dl and > 13 g/dl).
Slovenian: Bolniki so bili stratificirani glede na njihov izhodiščni hemoglobin (≤ 10 g/dl, > 10 do ≤ 13 g/dl in > 13 g/dl).
English: In the indication "increasing the yield of autologous blood": myocardial infarction or stroke in the month preceding treatment, unstable angina pectoris, increased risk of deep venous thrombosis such as history of venous thromboembolic disease.
Slovenian: Pri indikaciji "povečanje količine avtologne krvi": miokardni infarkt ali kap v preteklem mesecu, nestabilna angina pektoris, povečano tveganje globoke venske tromboze kot je venska tromboembolična bolezen v anamnezi.
English: Therefore your haemoglobin-levels and your blood pressure should be controlled.
Slovenian: Zato je treba nadzorovati nivo hemoglobina in krvni tlak.
English: Epoetin zeta is identical in its amino acid sequence and similar in carbohydrate composition to endogenous human erythropoietin that has been isolated from the urine of anaemic patients.
Slovenian: Epoetin zeta je, kar se zaporedja amino kislin in sestave ogljikovodikov tiče, identičen endogenemu humanemu eritropoetinu, ki so ga izolirali iz seča slabokrvnih bolnikov.
English: This medicine contains up to 0.5 mg phenylalanine in each dosage unit.
Slovenian: To zdravilo vsebuje do 0,5 mg fenilalanin v enoti odmerka.
English: In some pre-clinical toxicological studies in dogs and rats, but not in monkeys, erythropoietin therapy was associated with subclinical bone marrow fibrosis (bone marrow fibrosis is a known complication of chronic renal failure in humans and may be related to secondary hyperparathyroidism or unknown factors.
Slovenian: V nekaterih predkliničnih toksikoloških študijah na psih in mačkah, ne pa na opicah, je eritropietinsko terapijo spremljala subklinična fibroza kostnega mozga (fibroza kostnega mozga je pri ljudeh znan zaplet kronične ledvične odpovedi, ki je lahko povezana s sekundarnim hiperparatiroidizmom ali neznanimi faktorji.
English: In patients with chronic renal failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration recommended in section 4.2.
Slovenian: Pri bolnikih s kronično ledvično okvaro vzdrževalna koncentracija hemoglobina ne sme presegati zgornje meje priporočene ciljne koncentracije hemoglobina, ki je podana v poglavju 4.2.
English: Its use in this indication must be balanced against the reported risk of thromboembolic events.
Slovenian: Uporabo pri tej indikaciji moramo ovrednotiti glede na povečano tveganje tromboemboličnih zapletov.
English: Based on information available to date, correction of anaemia with erythropoietin in adult patients with renal insufficiency not yet undergoing dialysis does not accelerate the rate of progression of renal insufficiency.
Slovenian: Na osnovi podatkov, ki so trenutno na razpolago, popravki anemije z eritropoetinom pri odraslih bolnikih z ledvično nezadostnostjo, ki še niso na dializi, razvoja ledvične nezadostnosti ne pospešujejo.
English: If you are a patient with chronic renal failure, and particularly if you do not respond properly to Silapo, your doctor will check your dose of Silapo because repeatedly increasing your dose of Silapo if you are not responding to treatment may increase the risk of having a problem of the heart or the blood vessels and could increase risk of myocardial infarction, stroke and death.
Slovenian: Če ste bolnik s kronično ledvično okvaro; zlasti, če se na zdravilo Silapo ne odzivate ustrezno, bo zdravnik spremljal vaš odmerek zdravila Silapo, ker ponavljajoče se zviševanje odmerka zdravila Silapo, če se na zdravljenje ne odzivate, lahko poveča tveganje za težave s srcem ali krvnimi žilami in lahko poveč tveganje za srčni infarkt, možgansko kap in smrt.
English: Due to intra-patient variability, occasional individual haemoglobin values for a patient above and below the desired haemoglobin level may be observed.
Slovenian: Zaradi razlik med posameznimi bolniki je pri bolnikih občasno mogoče opaziti individualne vrednosti hemoglobina, ki so nad ali pod želeno koncentracijo hemoglobina.
English: This is characterised by a sustained decrease in haemoglobin despite an increase in Silapo dosage.
Slovenian: Značilno je tudi trajno zmanjšanje hemoglobina kljub povečanju odmerka zdravila Silapo.
English: Your doctor may decide that it is better for you to receive Silapo by injection under the skin (subcutaneous) rather than into a vein (intravenous).
Slovenian: Vaš zdravnik bo odločil, ali je za vas bolje, če zdravilo Silapo dobivate pod kožo (subkutano) injekcijo ali z injekcijo v veno (intravensko).
English: A randomised, double-blind, placebo-controlled, multicentre study evaluated the efficacy and safety of epoetin alfa in adult anaemic subjects with low- or intermediate-1-risk MDS.
Slovenian: V randomizirani, dvojno slepi, s placebom nadzorovani multicentrični študiji so ocenjevali učinkovitost in varnost epoetina alfa pri odraslih anemičnih preskušancih z MDS z nizkim ali srednjim-1 tveganjem.
English: If the solution is given into a vein, it should be injected over 1-5 minutes.
Slovenian: Če se raztopino daje v veno, naj injiciranje traja 1 - 5 minut.
English: Hyperkalaemia has been observed in isolated cases.
Slovenian: V posameznih primerih so opazili hiperkalemijo.
English: Epoetins are growth factors that primarily stimulate red blood cell production.
Slovenian: Epoetini so rastni dejavniki, ki primarno stimulirajo nastajanje rdečih krvničk.
English: Therefore, you should discuss the benefits of Silapo with your doctor, particularly if you are obese or have a history of blood clots/blood clotting disorders.
Slovenian: Zato se morate o koristih zdravila Silapo pogovoriti s svojim zdravnikom, posebno če ste debeli ali če ste že imeli krvne strdke ali motnje strjevanja krvi.
English: Other medicines and Silapo
Slovenian: Druga zdravila in zdravilo Silapo
English: If PRCA, a very rare condition, occurs, the Silapo therapy will be stopped and your doctor will determine the best course of action to treat the anaemia.
Slovenian: Če pride do PRCA, zelo redkega stanja, se bo zdravljenje z zdravilom Silapo prekinilo in vaš zdravnik bo odločil, kaj bo najboljši način za zdravljenje anemije.
English: In patients with chronic renal failure and clinically evident ischaemic heart disease or congestive heart failure, maintenance haemoglobin concentration should not exceed the upper limit of the target haemoglobin concentration.
Slovenian: Pri bolnikih s kronično ledvično okvaro in klinično jasno ishemično boleznijo srca ali s kongestivno srčno okvaro vzdrževana koncentracija hemoglobina ne sme presegati zgornje ciljne meje za koncentracijo hemoglobina.
English: In the randomised, double-blind, placebo-controlled, multicentre study 4 (4.7%) subjects experienced TVEs (sudden death, ischaemic stroke, embolism, and phlebitis).
Slovenian: V randomizirani, dvojno slepi, s placebom nadzorovani multicentrični študiji je pri 4 (4,7 %) preskušancih prišlo do TVE (nenadna smrt, ishemična kap, embolija in flebitis).
English: in moderately anaemic patients who are going to have surgery and prior to it, donate blood so that their own blood can be given to them during or after surgery (autologous pre-donation).
Slovenian: za zmerno slabokrvne bolnike, ki so pred operacijo in v ta namen pred njo darujejo kri, tako da jim bodo med operacijo dajali lastno kri (predhodno darovanje avtologne krvi).
English: Erythroid response during the first 24 weeks of the study was demonstrated by 27/85 (31.8%) of the subjects in the epoetin alfa group compared to 2/45 (4.4%) of the subjects in the placebo group (p<0.001).
Slovenian: Eritroidni odziv v prvih 24 tednih študije so dokazali pri 27/85 (31,8 %) preskušancev iz skupine, ki je prejemala epoetin alfa, v primerjavi z 2/45 (4,4 %) preskušancev iz skupine, ki je prejemala placebo (p < 0,001).
English: Subjects were stratified by serum erythropoetin (sEPO) level and prior transfusion status at screening.
Slovenian: Preskušance so stratificirali glede na raven eritropoetina v serumu (sEPO) in podatke o predhodnih transfuzijah ob presejanju.
English: The effect of epoetin alfa (300 IU/kg or 100 IU/kg) on the exposure to allogeneic blood transfusion has been evaluated in a placebo-controlled, double-blind clinical trial in non-iron deficient adult patients scheduled for major elective orthopaedic hip or knee surgery.
Slovenian: Učinek epoetina alfa (300 i.e./kg ali 100 i.e./kg) na izpostavljenjost alogenski transfuziji krvi so ocenili v s placebom nadzorovnem, dvojno slepem kliničnem preskušanju pri odraslih bolnikih brez pomanjkanja železa, ki imajo načrtovan večji elektivni ortopedski kirurški poseg na kolku ali kolenu.
English: If erythropoietin is given concomitantly with ciclosporin, blood levels of ciclosporin should be monitored and the dose of ciclosporin adjusted as the haematocrit rises.
Slovenian: Če se uporablja eritropoetin hkrati z ciklosporinom, je treba nadzorovati koncentracije ciklosporina v krvi in odmerek ciklosporina prilagajati s porastom hematokrita.
English: These may be the warning signs of a sudden rise in blood pressure, which requires urgent treatment.
Slovenian: To so lahko opozorilni znaki za nenadno zvišanje krvnega tlaka, ki zahteva takojšnje zdravljenje.