Academic literature on the topic 'AR Chemy app'

<strong><em>Abstract</em></strong> <em>The more modern and sophisticated technology of today are undergoing constant transformation. Every area of our life, including education, has changed as a result of contemporary computing technologies. Digital tools are used to enhance the traditional teaching method. Additionally, a lot of software with varied functions is being used. A single one of them is augmented reality (AR). AR gives kids access to real-world experiences. A knowledge-based society, where knowledge is a tremendous power, economy, and potency of an individual and the benefit of a country, has benefited greatly from the advances in science and technology and their application. Its greatness and expansion both have a magnificent detonation. To access and effectively use this rapidly developing technology, we require innovative knowledge. It necessitates total access to and control over the knowledge acquisition process. With the aid of information and communication technological science, it is possible. Over the past ten years, augmented reality (AR) interfaces have proliferated, with an increase in user-based trials. Chemistry note cards have long been a mainstay for remembering new concepts; with AR, they now offer greater content for learning. An open-source computer tracking framework called ARToolkit is used to build powerful augmented reality apps. A digital content repository with the construction of coursework, learning games and simulations, augmented reality, and virtual reality will be developed with efficiency and perfection, according to the National Education Policy (NEP, 2020). The current status, various device types, hardware, software, applications, and content for augmented reality are discussed in this paper.</em>

Introduction Bruton's tyrosine kinase inhibitors (BTKi) have improved 1 st line therapy efficacy in elderly (Wang NEJM 2022) and young, fit, MCL-the latter with intermittent dosing during RCHOP in an alternating RCHOP/cytarabine-based regimen (Dreyling Blood 2022). However direct combination of BTKi &amp; intensive chemo is toxic in DLBCL studies. (Kuruvilla Haematol Oncol 2017). The highly selective BTKi, acalabrutinib (A), has proven efficacy and tolerability in relapsed MCL (Wang Lancet 2018). RDHAOx chemotherapy (rituximab, dexamethasone, cytarabine, oxaliplatin) prior to ASCT provides a complete response (CR) rate of 77% and favourable toxicity compared to many induction regimens (Le Gouill Blood 2017). Furthermore, Obinutuzumab-DHAP yields undetectable minimum residual disease (MRD) in 85% of young MCL patients. (Le Gouill Haematol Oncol 2019). Here we report the primary endpoint from the Australasian Leukaemia &amp; Lymphoma Group phase 2 ‘WAMM’ trial exploring a ‘sandwich’ model of an acalabrutinib-rituximab (AR) ‘window’ before RDHAOx +/- ASCT, followed by fixed-duration AR-maintenance to improve therapy response and minimise additional toxicity. Methods NHL33'WAMM' (ACTRN12619000990123) is a multicentre single-arm phase 2 trial. Key eligibility included: age 18-70 years, untreated histologically-proven stage II-IV MCL, ECOG&amp;lt;2; no contraindications to ASCT or BTKi. Pts received 2 cycles of AR (AR window); ‘A’ dose; 100mg BD PO, ‘R’ dose; 375mg/m 2 IV (day 1) every 4 weeks, followed by RDHAOx x4 cycles. Those with an objective response (CR or partial response-PR) underwent BEAM ASCT (carmustine, etoposide, cytarabine, melphalan) then AR maintenance (A; 1yr continuous &amp; R; 3-monthly x 8 cycles). Those who did not undergo BEAM ASCT were able to remain on study and proceed to maintenance AR in the event of ongoing response. Co-primary endpoints (EP) were safety; defined by lack of prohibitive toxicity causing treatment cessation AND PET-determined complete response (CR) rate after AR+RDHAOx. Secondary EP include overall response rates (ORR), toxicity, overall survival (OS) &amp; progression-free survival (PFS), MRD negativity rates and quality of life. Only Grade 3+ toxicity related to acalabrutinib was collected during the ASCT period. Baseline whole exome sequencing was performed to identify mutations, MRD analysis was done by LymphoTrack® Dx and MRD Assay platform (Invivoscribe, Inc) using Illumina® MiSeq. This study was the first Australian blood cancer trial to use telehealth and a ‘hub-and-spoke’ transplant model. Results 44 pts were enrolled from Sept 2020 to Apr 2022 (43 evaluable for the primary endpoint). Baseline characteristics were typical of a young MCL cohort: median age 59 years (Interquartile range 54-64), 77% were male, ECOG was 0-1 in 98%, 84% had stage IV, lactate dehydrogenase was elevated in 35%, Ki-67 &amp;gt;30% in 66% and blastoid/pleomorphic histology 9%. TP53 by NGS will be reported at presentation. CR rate post AR+RDHAOx induction was 88%; (95%CI 72-95) with ORR 95% and no prohibitive toxicity. AR window ORR was 93% (CR 57%). MRD negativity was achieved in 18% (7/38) post AR window, and 94% (34/36) post RDHAOx. 43 patients remained evaluable for response after R-DHAOX and pre-maintenance with 35 (80%) who underwent ASCT and 38 (86%) who commenced AR maintenance; 7 remain on maintenance. Response in specific subgroups will be reported at the meeting. At data lock, 35 pts (81%) experienced ≥1 G3+ adverse events during induction or maintenance phases, most common were neutropenia (58% of pts), febrile neutropenia (27%), thrombocytopenia (25%), diarrhea (14%). No G5 treatment-related events have occurred to date. There have been 22 SAEs, most common were COVID (3), febrile neutropenia (2) and fever (2). 5 deaths have been reported: 4 in pts with progressive disease and 1 COVID pneumonitis during AR maintenance. After a median follow up of 22 months (range 17-28m), the 2-year OS was 89%. Analysis of survival, quality of life and biomarkers will be reported with more mature follow up. Conclusion AR delivered in a sandwich approach is active and safe. An AR window yields a high ORR and compared to historical studies, improves post-chemo induction CR rates and MRD negativity. A telehealth model allowed rapid recruitment in a rare cancer.

Appropriate trafficking of the β1-adrenergic receptor (β1-AR) after agonist-promoted internalization is crucial for the resensitization of its signaling pathway. Efficient recycling of the β1-AR required the binding of the protein kinase A anchoring protein-79 (AKAP79) to the carboxyl terminus of the β1-AR (Gardner, L. A., Tavalin, S. A., Goehring, A., Scott, J. D., and Bahouth, S. W. (2006) J. Biol. Chem. 281, 33537-33553). In this study we show that AKAP79 forms a complex with the type 1 PDZ-binding sequence (ESKV) at the extreme carboxyl terminus of the β1-AR, which is mediated by the membrane-associated guanylate kinase (MAGUK) protein SAP97. Thus, the PDZ and its associated SAP97-AKAP79 complex are involved in targeting the cyclic AMP-dependent protein kinase (PKA) to the β1-AR. The PDZ and its scaffold were required for efficient recycling of the β1-AR and for PKA-mediated phosphorylation of the β1-AR at Ser312. Overexpression of the catalytic subunit of PKA or mutagenesis of Ser312 to the phosphoserine mimic aspartic acid both rescued the recycling of the trafficking-defective β1-ARΔ PDZ mutant. Thus, trafficking signals transmitted from the PDZ-associated scaffold in the carboxyl terminus of the β1-AR to Ser312 in the 3rd intracellular loop (3rd IC) were paramount in setting the trafficking itinerary of the β1-AR. The data presented here show that a novel β1-adrenergic receptosome is organized at the β1-AR PDZ to generate a scaffold essential for trafficking and networking of the β1-AR.

134 Background: Androgen receptor (AR) signaling is the principal driver of PC at all stages. CC-94676 (BMS-986365) is a heterobifunctional, first-in-class, orally bioavailable AR LDD designed to induce rapid, sustained, and highly selective AR degradation in pts who progressed on standard of care therapies. We report initial results from an open-label, multicenter study, NCT04428788, evaluating CC-94676 in pts with progressive mCRPC. Methods: Pts with mCRPC who progressed on androgen deprivation therapy, ≥ 1 second generation hormonal therapy (eg, enzalutamide [enza], abiraterone [abi], darolutamide, and apalutamide) and taxane chemotherapy (chemo) (unless refused or not indicated) were enrolled to evaluate the safety, tolerability, PK/PD, and preliminary efficacy of CC-94676. Escalation doses evaluated were 100–1200 mg QD and 600–900 mg BID; expansion doses were 600 mg QD and 400–900 mg BID. Results: As of Aug 21, 2023, 95 pts received CC-94676 (median age 71 yrs) with a median of 5 (range 2–12) prior therapies, including enza (80%), abi (72%), both enza &amp; abi (56%), and chemo (56%) (docetaxel 55%; cabazitaxel 20%). There were no ≥ Grade (G) 4 treatment-related adverse events (TRAEs) or discontinuations due to TRAEs. Of 27 pts treated in escalation, treatment (Tx) was well tolerated; 2 pts had non-serious G3 TRAEs at doses ≥ 800 mg QD, which were manageable with dose modifications. One dose-limiting toxicity of asymptomatic QTc prolongation was observed at 900 mg BID and resolved with dose interruption. The maximum tolerated dose was not reached. Of 68 pts treated in expansion, the most common TRAEs were dose-dependent: QTc prolongation (asymptomatic) (43%; G3: 9%), bradycardia (31%; ≥G3: none), and fatigue (24%; ≥G3: none). G3 TRAEs were manageable with dose modifications. The rate of pts with confirmed PSA reductions ≥ 30% (PSA30) increased dose-dependently from 400 to 900 mg BID. 23/68 (34%) pts across all dose levels achieved ≥ PSA30. At 900 mg BID, 11/20 (55%) pts showed PSA30; 7/20 (35%) and 2/20 (10%) had confirmed PSA declines of ≥50% and ≥90%, respectively. PSA responses and radiographic tumor shrinkage occurred across all dose levels, including in pts with AR wildtype (WT) , amplifications, and mutations (by cfDNA), and in heavily pretreated pts who progressed on abi, enza, and chemo. At 900 mg BID, the median duration of Tx was 182 days (range 21-448) and 9/20 (45%) pts remained free of radiographic progression with treatment ongoing at 6 months. Conclusions: CC-94676 is well tolerated with a manageable safety profile. CC-94676 shows promising and prolonged clinical activity in heavily pretreated mCRPC pts who progressed on abi, enza, and chemo with activity seen in pts with tumors expressing WT and mutant ARs. Selection of the recommended phase 2 dose is ongoing. Clinical trial information: NCT04428788 .

252 Background: Liquid biopsy assays in mCRPC are utilized for treatment eligibility of PARP inhibitors (HRR) and Pembrolizumab (MSI High). These ctDNA targeted gene panels provide translational data beyond gene mutations. Tumor Fraction (TF), the percentage of cfDNA from tumor, is a promising prognostic efficacy biomarker in pre-chemo mCRPC, and a potential predictive biomarker to post-chemo PSMA radioligand therapy. Methods: We analyzed ctDNA run with Illumina-TSO500 from the CA209-7DX Ph3 mCRPC trial (Nivo+chemo vs. Chemo in chemo-naïve mCRPC) to determine: TF at baseline or changes at Cycle6 Day1 (C6D1). TF at each timepoint was determined through the maximum somatic allelic frequency. Results: We present a combined analysis of treatment arms as both showed similar association between clinical outcomes and TF levels as well as clearance. Out of 1030 ITT patients TF data was available for 527 (51%) patients. Patients in the highest TF tertile had TF of ≥4.6% and TF&lt;0.3% for the lowest tertile. Patients in the lowest TF tertile had 10 months longer overall survival (OS) to the highest TF tertile (p&lt;0.001). Patients in the highest TF tertile demonstrated higher hazard ratio for OS (HR 3.42,[2.34-4.98] p&lt;0.001) and rPFS (HR 1.95 [1.47-2.59], p&lt;0001) over lowest tertile. This differential was maintained across arms and indicates that TF is a strong prognostic biomarker. High TF outperformed common stratification factors (prior exposure to chemo in CSPC or novel ARPIs) for poor prognostication in a multivariate analysis. TF high patients have higher rates of AR-Amp/AR-LBD mutations (72.6%) than TF low (28.8%). Patients with TF clearance, defined as TF &lt; 1% at C6D1 had 8 months mOS advantage over patients with a TF &gt;1% at baseline and on-treatment. TF clearance strongly correlated with OS (HR=0.42 [0.28-0.62], p&lt;0.001), rPFS benefit (HR=0.24 [0.17-0.34], p&lt;0.001) and PSA response (28% vs. 62%) regardless of treatment arm. Conclusions: This data advocates for plasma TF as a robust prognostic biomarker and as a potential stratification opportunity in mCRPC clinical trials. TF clearance may act as an early indicator of treatment response and hence can be an important monitoring tool for mCRPC patient management. Clinical trial information: NCT04100018 .

Abstract. Winter fog and severe aerosol loading in the boundary layer over northern India, particularly in the Indo-Gangetic Plain (IGP), disrupt the daily lives of millions of people in the region. To better understand the role of aerosol–radiation (AR) feedback on the occurrence, spatial extent, and persistence of winter fog, as well as the associated aqueous chemistry in fog in the IGP, several model simulations have been performed using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). While WRF-Chem was able to represent the fog formation for the 23–24 December 2017 fog event over the central IGP in comparison to station and satellite observations, the model underestimated PM2.5 concentrations compared to the Central Pollution Control Board (CPCB) of India monitoring network. While evaluating aerosol composition for fog events in the IGP, we found that the WRF-Chem aerosol composition was quite different from measurements obtained during the Winter Fog Experiment (WiFEX) in Delhi, with secondary aerosols, particularly the chloride aerosol fraction, being strongly underpredicted (∼ 66.6 %). Missing emission sources (e.g., industry and residential burning of cow dung and trash) and aerosol and chemistry processes need to be investigated to improve model–observation agreement. By investigating a fog event on 23–24 December 2017 over the central IGP, we found that the aerosol–radiation feedback weakens turbulence, lowers the boundary layer height, and increases PM2.5 concentrations and relative humidity (RH) within the boundary layer. Factors affecting the feedback include loss of aerosols through deposition of cloud droplets and internal mixing of absorbing and scattering aerosols. Aqueous-phase chemistry increases the PM2.5 concentrations, which subsequently affect the aerosol–radiation feedback by both increased mass concentrations and aerosol sizes. With aerosol–radiation interaction and aqueous-phase chemistry, fog formation began 1–2 h earlier and caused a longer fog duration than when these processes were not included in the WRF-Chem simulation. The increase in RH in both experiments was found to be important for fog formation as it promoted the growth of aerosol size through water uptake, increasing the fog water content over the IGP. The results from this study suggest that the aerosol–radiation feedback and secondary aerosol formation play an important role in the air quality and the intensity and lifetime of fog over the IGP, yet other feedbacks, such as aerosol–cloud interactions, need to be quantified.

Abstract Metastatic prostate cancer is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and are therefore sensitive to androgen deprivation therapies. However, eventual resistance to standard medical castration and secondary chemotherapies including next-generation AR-targeting agents like abiraterone or enzalutamide and taxanes (Docetaxel or cabazitaxel) is nearly universal. Further, neuroendocrine PCa or NEPC, a poorly differentiated aggressive variant of PCa that lacks AR expression, and the presence of cancer stem-like cells with self-renewal and differentiation (epithelial to mesenchymal trans-differentiation or EMT) capacities significantly contribute to the development of clinically most aggressive and lethal variants of PCa. Endogenous Ras/ERK/MAPK signaling is known to drive prostate tumor formation, cancer progression, cell migration, and the acquisition of mesenchymal phenotype (EMT) in metastatic prostate cancers. Ras family members are responsible for modulating the function of most of the receptors upregulated in advanced PCa, including AR, so that AR can be functional even in the absence of physiologic levels of androgen. Previous studies have reported that the NSAID, sulindac, inhibits Ras-induced transformation and directly binds Ras. In this study, we show that a non-COX inhibitory sulindac derivative, ADT-007, is a potent drug candidate against lethal PCa. First, we performed single-cell RNA sequencing as a biomarker-based drug screen and showed that chemo-resistant, drug-tolerant, stem-cell-like PCa cell clusters had high expression of Ras genes, indicating that the Ras inhibitor, ADT-007, may be effective in targeting these aggressive subclones. Next, using several cell-based assays on a large panel of lethal PCa cell lines representing metastatic castration-resistant PCa (mCRPC), NEPC as well as African American ancestry, we showed that ADT-007 is highly effective as a single-agent and in combination with taxanes. Combination index values were &amp;lt;0.7, and BLISS scores were &amp;gt;10, indicating very high synergy. Finally, using pre-vs-post-treatment bulk RNAseq, we demonstrated that ADT-007 is indeed effective in downregulating KRas and NRas in a dose-dependent manner. In addition, ingenuity pathway analysis (IPA) predicted significant downregulation of cell cycle, DNA replication, CCND1, AR, and the lncRNA ELDR, and upregulation of autophagy and interferon pathway genes, and the microRNA miR-96. Finally, using PCa patient datasets, we showed that ADT-007 is potentially capable of reversing the expression of several genes associated with biochemical recurrence. Thus, our results show that ADT-007 is a novel drug candidate that circumvents subclonal aggressiveness, drug resistance, and stemness in lethal PCa through simultaneous inhibition of multiple oncogenic factors/pathways. Citation Format: Taraswi Mitra Ghosh, Adam B. Keeton, Xi Chen, Salsabil Ahmed, Razan S. Waliagha, Gary A. Piazza, Amit K. Mitra. Validation of a novel pan-Ras inhibitor, ADT-007, against lethal variants of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1638.

237 Background: AA/P is an approved treatment for mCRPC but there are no known predictive markers of response or resistance. We conducted a prospective trial to evaluate if Androgen Receptor (AR) &amp; AR-variant (ARV) expression in tissue metastases can predict resistance to AA/P. Methods: mCRPC stage patients (pts) initiating pre-chemo AA/P underwent metastatic site biopsies prior to (pre-AA/P) and after 12 weeks of treatment. Composite progression at 12 weeks, (primary endpoint) was evaluated with PSA, RECIST, bone scan and symptoms (per PCWG2). mRNA expressions of pre-AA/P ARFL, ARV3, ARV7, ARV9, ARV23, ARV45, four cell cycle division genes, Chromogranin-A (CHGA) together with PSA/testosterone levels, Gleason Score (GS) at initial diagnosis; high versus low volume disease; time from starting hormone therapy to mCRPC stage and serum CHGA levels were evaluated using a logistic regression model for predicting resistance at 12 weeks of therapy. A final multivariate model fitted only those factors thought to be clinically relevant or with an entry threshold of p ≤ 0.3 in univariate analysis. Results: Between 6/2013 &amp; 3/2015, 82 pts were enrolled of which 52 had complete mRNA expression &amp; disease assessment data at the12-week time point for analysis. Median age of the cohort was 72.5 yrs (IQR: 68.5-78); median pre-AA/P PSA was 18 ng/ml (IQR: 8.1- 46.6); GS distribution at initial diagnosis for GS 2-6; 7; 8-10 was 11; 14; 27 respectively. Progression was observed in 21/52 pts after 12 weeks. At the univariate level elevated pre-AA/P expression of ARV3 (p = 0.08), ARV7 (p = 0.26), ARV9 (p = 0.04), and cell division cycle gene CDC45 (p = 0.19) along with GS at diagnosis (p = 0.29) met the threshold for inclusion into multivariate analysis. Elevated expression of pre-therapy ARV9 in metastases alone was associated with progression at 12 weeks (OR: 3.9; CI 1.07 – 14.16; C-Index: 0.63). The 12-week biopsy of pts with progression had increased ARV9 mRNA expression compared to pts responding at 12 weeks (p = 0.14). Conclusions: Increased ARV9 mRNA expression in metastases is associated with early resistance to AA/P. This observation will need further validation in comparable datasets. Clinical trial information: NCT #0195364.

SummaryPlatelet activation results in shape change, aggregation, generation of thromboxane A2, and release of granule contents. We have recently demonstrated that secreted ADP is essential for thromboxane A2-induced platelet aggregation (J. Biol. Chem. 274: 29108-29114, 1999). The aim of this study was to investigate the role of secreted ADP interacting at P2 receptor subtypes in platelet secretion. Platelet secretion induced by the thromboxane A2 mimetic U46619 was unaffected by adenosine-3’phosphate-5’-phosphate, a P2Y1 receptor selective antagonist. However, AR-C66096, a selective antagonist of the P2T AC receptor, inhibited U46619-induced platelet secretion, indicating an important role for Gi signaling in platelet secretion. Selective activation of either the P2T AC receptor or the α2A adrenergic receptor did not cause platelet secretion, but potentiated U46619-induced platelet secretion. SC57101, a fibrinogen receptor antagonist, failed to inhibit platelet secretion, demonstrating that outside-in signaling was not required for platelet secretion. Since Gi signaling results in reduction of basal cAMP levels through inhibition of adenylyl cyclase, we investigated whether this is the signaling event that potentiates platelet secretion. SQ22536 or dideoxyadenosine, inhibitors of adenylyl cyclase, failed to potentiate U46619-induced primary platelet secretion, indicating that reduction in cAMP levels does not directly contribute to platelet secretion. Wortmannin, a selective inhibitor of PI-3 kinase, minimally inhibited U46619-induced platelet secretion when it was solely mediated by Gq, but dramatically ablated the potentiation of Gi signaling. We conclude that signaling through the P2TAC receptor by secreted ADP causes positive feedback on platelet secretion through a PI-3 kinase pathway.

Triple-negative breast cancer (TNBC), characterized by the absence or low expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), is the most aggressive subtype of breast cancer. TNBC accounts for about 15% of breast cancer cases in the U.S., and is known for high relapse rates and poor overall survival (OS). Chemo-resistant TNBC is a genetically diverse, highly heterogeneous, and rapidly evolving disease that challenges our ability to individualize treatment for incomplete responders and relapsed patients. Currently, the frontline standard chemotherapy, composed of anthracyclines, alkylating agents, and taxanes, is commonly used to treat high-risk and locally advanced TNBC. Several FDA-approved drugs that target programmed cell death protein-1 (Keytruda) and programmed death ligand-1 (Tecentriq), poly ADP-ribose polymerase (PARP), and/or antibody drug conjugates (Trodelvy) have shown promise in improving clinical outcomes for a subset of TNBC. These inhibitors that target key genetic mutations and specific molecular signaling pathways that drive malignant tumor growth have been used as single agents and/or in combination with standard chemotherapy regimens. Here, we review the current TNBC treatment options, unmet clinical needs, and actionable drug targets, including epidermal growth factor (EGFR), vascular endothelial growth factor (VEGF), androgen receptor (AR), estrogen receptor beta (ERβ), phosphoinositide-3 kinase (PI3K), mammalian target of rapamycin (mTOR), and protein kinase B (PKB or AKT) activation in TNBC. Supported by strong evidence in developmental, evolutionary, and cancer biology, we propose that the K-RAS/SIAH pathway activation is a major tumor driver, and SIAH is a new drug target, a therapy-responsive prognostic biomarker, and a major tumor vulnerability in TNBC. Since persistent K-RAS/SIAH/EGFR pathway activation endows TNBC tumor cells with chemo-resistance, aggressive dissemination, and early relapse, we hope to design an anti-SIAH-centered anti-K-RAS/EGFR targeted therapy as a novel therapeutic strategy to control and eradicate incurable TNBC in the future.

"Prefață: Consiliere și mentorare cu impact Călăuzirea spirituală: de la „avva” Antichității la mentorul de azi Sfântul apostol Pavel le scria romanilor: „Dar cum vor chema pe Acela în care n-au crezut? Și cum vor crede în Acela despre care n-au auzit? Și cum vor auzi despre El, fără ca cineva să predice? Și cum vor predica, dacă n-au fost trimiși? Astfel, credința vine din cele auzite, iar cele auzite, prin Cuvântul Lui Dumnezeu.” (Romani 10: 14-15). Nimeni n-a plecat la propovăduire de capul lui. 1. Inițial, Isus „a chemat pe cine a vrut” (chemarea; vocația divină: gr. kaleo; lat. voco/are = a chema); 2. apoi, „ei au venit la El și a rânduit dintre ei 12, ca să-i aibă cu Sine” (răspunsul personal: voluntar și prompt [lat. protinus = îndată]; asumarea vocației apostolice și „ucenicia” alături de Isus timp de trei ani; gr. mathitevo = a fi discipol; a învăța; lat. discipulus); și 3. în final, Isus „i-a trimis să predice” (misiunea apostolică; gr. apo/stello; lat. mitto/ere = a trimite; missio/onis = trimitere; gr. kirysso = a propovădui; „a face o proclamație în calitate de herald”; un „mesager al Domnului”; gr. kyr = domn) [Marcu 3:13-14]. Chemare, ucenicie, trimitere..., toate acestea s-au petrecut „la împlinirea timpului” (Galateni 4:4), într-un moment de cumpănă al omenirii, cum ar zice E. Cioran: „Pe culmile disperării”, când „Poporul care stătea în întuneric, a văzut o mare Lumină și, celor care zăceau în ținutul și în umbra morții, le-a răsărit Lumina” (Matei 4:16) „transfigurării cosmice” (Cioran) mesianice. Isus n-a venit într-o lume pregătită să-L primească, ci într-o lume bulversată, disperată și în așteptare... Nu era o lume mai dreaptă, mai bună, mai credincioasă, mai morală, mai cultă, mai catehizată, mai primitoare decât cea de azi. Dar Isus n-a ținut cont de nimic din toate astea, ci pur și simplu a venit să-și îndeplinească „misiunea”: a învățat, a vindecat boli incurabile, a înviat persoane trecute în „viața de apoi”, a iertat, a exorcizat „demonii” multor patimi, a dat sens multor vieți, a provocat, a contestat formalismele Templului, cărturarilor și fariseilor, a declanșat furia mai marilor vremii și nu a fugit de supliciul și „rușinea” crucii. Într-un fel, la (răs)crucea vremurilor de azi, lucrurile par a se suprapune cu cele din timpul lui Isus. Trăim într-o lume complet debusolată, secularizată, nihilistă, agnostică, sceptică, indiferentă, relativistă, dezumanizată, lacomă și nesătulă, buimacă, parcă „fără istorie spirituală și fără viitor”, ostilă Celui de Sus și refractară oricărei morale, o epocă a indiscreției și lipsei de pudoare, a pornografiei, traficului de carne vie, vânzărilor de armament, droguri etc., fără sentimentul păcatului (Morale sans péché, dr. Hesnard, 1954), fără pic de rușine, fără valori, direcție, sens și destinație spirituală. Dumnezeu ne-a adus de la haos (abis, „tohu wa bohu” = o lume „fără formă și goală”; „fără cap și fără coadă”) la kosmos (ordine, viață, „căpătâi”), dar noi, parcă tributari „vocației entropiei”, mergem ireversibil către neant, nonsens și autodistrugere. Dumnezeu ne-a dăruit Viața, dar noi, incapabili să-i descifrăm farmecul, bucuria, valoarea și sensul, ne-o suprimăm sau ne-o irosim în nimicnicie. Ne-a dăruit Iubirea, dar ura, intoleranța și resentimentele ne stăpânesc. „Lumina a venit în lume, dar oamenii au iubit mai mult întunericul decât lumina, pentru că faptele lor erau rele.” (Ioan 3:19). Nu suntem cu nimic mai buni peste 2000 de ani decât atunci, dimpotrivă! Dar, în loc să stăm și să ne lamentăm continuu, mai bine căutăm soluții. Omul sfințește locul! Tuturor acestor provocări vor trebui să le facă față duhovnicii, mentorii, cateheţii și toți învățătorii spirituali de azi. O teologie de manual, scolastică, teoretică, stearpă și polemicile noastre confesionaliste sunt de mult depășite. Cum „imputa” ironic un student profesorului de dogmatică: „Dom’ profesor, cred că nici Dumnezeu nu știe despre El atâtea câte ați scris dumneavoastră în manualul acesta!” Termeni, dogme, erezii, speculații filosofice, dispute – la ce servesc toate astea? „Nimic nu e mai sărac decât cugetarea care, stând afară de Dumnezeu, filosofează despre Dumnezeu.” (Diadoh, episcop al Foticeei, sec. V). Azi, e nevoie de creștini autentici și mărturisitori adevărați (gr. martirevo = a mărturisi; de aici și termenul de „martir”) într-o relație vie cu Dumnezeu, „din interiorul Lui”, în Duhul Lui, nu doar de niște transmițători de cunoștințe teologice exterioare, mereu puși pe harță pentru monopolul (exclusivismul) și „drepturile de autor” asupra „adevărului” divin. Vremea polemicilor sterile a apus. Lumea nu mai are nevoie să afle „sexul îngerilor”! E nevoie de o Întâlnire adevărată cu Dumnezeu, nu doar la nivelul minții și speculațiilor teologice, ci și la nivelul inimii și al spiritului. Un consilier sau mentor spiritual asta va trebui să facă, să-l conducă pe omul zilelor de azi la Marea Întâlnire existențială și spirituală cu Dumnezeu. „Oare poate un orb să călăuzească pe un alt orb? Nu vor cădea amândoi în groapă?” (Luca 6:39). Avem nevoie de duhovnici adevărați, de consilieri adevărați, de mentori spirituali adevărați, cu pregătire umană, teologică și viață spirituală pe măsură, care să înțeleagă omul de azi cu toate problemele, slăbiciunile și ezitările lui, nu de triumfaliști „îmbelferiţi ai spiritului”, de legaliști, formaliști, moraliști de mucava care să te trateze de pe poziții de superioritate, suficiență și omnisciență. Avem nevoie de călăuze spirituale umane, calde, autentice, vii care să „nu ne dea lecții de morală ieftină” și de „auto-izbutită soteriologie”. Nu e nevoie de „experți” care să ni se insinueze drept „modele” și „păstori” ai unei turme paraplegice și oarbe, ci de oameni adevărați cu inimă caldă și mare, cu care să putem intra într-un dialog real, de la om la om, de la suflet la suflet, cu Dumnezeul cel Viu prezent în mijlocul nostru. Predica publică e una, relația de îndrumare spirituală, de consiliere sau de mentorat este alta. Este o relație particulară, de la om la om, cu o forță de impact soteriologic imensă: o adevărată „chirurgie spirituală” în care omul își oferă mentorului spiritual inima deschisă ca „pe tavă” cu toată încrederea. De măiestria și responsabilitatea duhovnicului, consilierului sau mentorului spiritual depinde „reușita operației” și felul în care este „suturată” incizia. Din păcate, mulți au rămas profund dezamăgiți și debusolați după „întâlnirea” cu unele „pseudo-călăuze” sau „mercenari” implicați în acest câmp psihologic și spiritual extrem de fragil. Predica te poate atinge parțial, dar cuvântul adresat direct, de la inimă la inimă, n-are cum să nu-ţi trezească sentimente, întrebări, idei, aspirații puternice. Aceasta și era relația directă dintre avva (maestrul spiritual) și ucenic, încă din antichitatea creștină, și către asta tindem și acum, spre o neo-evanghelizare sau re-încreştinare autentică (nu îndoctrinare sau prozelitism) a omului, prin comunicarea față în față cu mentorul, un om mai experimentat, pregătit (psihologic și spiritual), cu învățăcelul, în curs de formare, pentru a-l smulge din marasmul și pericolele societății atee despre care vorbeam mai sus. Mai trebuie doar să înțelegem că, azi, această relație spirituală de călăuzire este cumva „pe picior de egalitate”. Nimeni nu se consideră superior nimănui, doar „maestrul” spiritual este dispus și disponibil să (se) investească în „discipol”, în beneficiul orientării lui existențiale și mântuirii. Aceasta înseamnă „artă” și autenticitate spirituală! Volumul de față, Consiliere și mentorare cu impact, ca, de altfel, întreaga colecție Autentic, urmăreşte obținerea unor mărturii adevărate ale unor persoane autentice, care să le fie de folos în orientarea și formarea oamenilor dispuși să-și caute calea și rostul lor spiritual. Așa cum, deja, ne-a obișnuit apariția primului volum, Copilărie și parentalitate cu impact, structura celui de față este la fel de coerentă, variată și interesantă cum, nu mă îndoiesc nicio clipă, vor fi și cele ce vor urma. Coordonatoarea volumului și a colecției, doamna conf. univ. dr. Patricia Runcan, un manager cultural excelent și, la rându-i, un om spiritual autentic, nu se dezice, nici de această dată, de stilul ei „nemțesc”, precis, pedant și de chemarea/menirea pe care i-a dat-o Dumnezeu: de a învăța în școală, de a mărturisi în/prin Biserică și de a scrie mesajul divin celor dispuși să-l asculte. Susțin și încurajez, cu tot sufletul, această minunată inițiativă a colecției Autentic și sper să dea roade cât mai bogate și îndelungate! Conf. univ. dr. Eugen Jurca "