Tolerability Issues Research Articles

Long-term outcomes of S-1 monotherapy in stage IIIA gastric cancer with small tumors and low nodal involvement

BackgroundIn Japan, adjuvant chemotherapy with docetaxel/S-1 is recommended for stage III gastric cancer. However, this regimen may not be suitable for all patients due to toxicity and tolerability issues, particularly in older individuals or those with comorbidities. This study aimed to explore prognostic factors in stage IIIA gastric cancer and assess long-term outcomes in patients treated with S-1 monotherapy after curative gastrectomy.MethodsWe retrospectively analyzed 73 patients with stage IIIA gastric cancer (UICC 7th edition) who underwent curative gastrectomy and received postoperative adjuvant S-1 monotherapy between 2005 and 2018.Various prognostic factors, including preoperative (age, sex, BMI, tumor markers), perioperative (surgical approach, operative duration, blood loss, complications), and tumor-related variables (tumor size, lymph node status, histological features), were analyzed. Recurrence-free survival (RFS) was the primary endpoint, and cut-off values were determined using ROC analysis. Cox proportional hazards models were used for univariate and multivariate analyses.ResultsThe 3- and 5-year RFS rates were 71.7% and 64.3%, respectively. Multivariate analysis identified smaller tumor size (≤ 55.0 mm, P = 0.006) and lower lymph node positivity rate (≤ 0.079, P = 0.008) as independent favorable prognostic factors.ConclusionS-1 monotherapy may be associated with favorable long-term outcomes in selected patients with stage IIIA gastric cancer who have small tumors and low lymph node positivity rates. While these results are encouraging, they should not be interpreted as a rationale for broadly recommending S-1 monotherapy. Further studies are needed to define its role in individualized treatment strategies.

Molecular Insights into the Interaction of Orexin 1 Receptor Antagonists: A Comprehensive Study Using Classical and Quantum Computational Methods.

Sleep disorders, such as insomnia and narcolepsy, significantly impact quality of life. They are often associated with long-term health consequences, including cardiovascular disease, immune dysfunction, and cognitive impairment. While traditional treatments, such as sedatives and hypnotics, can be effective, they are limited by issues of tolerance and dependence. The orexinergic system, particularly the orexin 1 receptor (OXR1), has emerged as a promising therapeutic target due to its central role in regulating sleep-wake cycles. In this study, we investigate the molecular interactions of three OXR1 antagonists-daridorexant, lemborexant, and suvorexant-using an integrated computational approach combining molecular dynamics (MD) simulations, density functional theory (DFT) calculations, and the molecular fractionation with conjugate caps (MFCC) methodology. The MFCC approach enabled the precise quantification of interaction energies between ligands and key receptor residues, providing detailed insights into the contributions of specific amino acids to binding stability. Our results reveal that residues such as GLU204, HIS216, and ASN318 play critical roles in stabilizing ligand-receptor interactions, with a marked decrease in binding energy magnitude as dielectric constants increase. Daridorexant exhibited the strongest interaction energy, driven by hydrogen bonds and hydrophobic contacts, while lemborexant and suvorexant showed distinct stabilization patterns mediated by hydrophobic interactions. These findings provide a robust molecular basis for the rational design of next-generation OXR1 antagonists with improved efficacy and safety profiles. By elucidating drug-receptor interactions at the atomic level, this research underscores the impact of integrated computational approaches in drug discovery. It supports the development of precise targeted therapies for sleep disorders.

Long-term outcomes of Aripiprazole long-acting injectable: a 10-year mirror image study of patient acceptability and treatment effectiveness

Relapses are frequent in schizophrenia and other psychotic disorders. While long-acting injectable antipsychotics (LAIs) are effective in preventing hospital admissions and improving adherence and patient outcomes, they are still under-utilised. Furthermore, evidence from newer formulations and longitudinal studies, despite their commonly long-term use, remains limited. To address this scarcity of data, this study aims to evaluate the long-term effectiveness and acceptability of once-monthly Aripiprazole long-acting injectable (ALAI), the only third-generation antipsychotic available in long-acting formulation. In this pragmatic, independent, ten-year mirror-image study conducted within a large urban mental health service in London, UK, we assessed hospital admission rates and treatment retention over 5 years following ALAI initiation in a naturalistic adult cohort. Frequency and length of hospitalisations in the 5 years pre- and post-initiation were recorded using electronic records, as were discontinuation rates and reasons. Separate analyses were performed comparing outcomes between treatment completers and discontinuers, as well as between those with schizophrenia vs other diagnoses. In total, 135 patients were included in the study (63% with Schizophrenia, 37% with other diagnoses). The discontinuation rate was 47% at 5 years (23.7%, 13.6%, 7.9%, 7.3% and 5.3% in years 1 to 5 respectively). Among the 53% who completed 5 years of ALAI treatment, we observed an 88.5% reduction in mean number (1.57 to 0.18, p < 0.001) and a 90% reduction in mean length of hospitalizations compared to 5 years pre-ALAI initiation (103 to 10 days, p < 0.0001). Median admissions and length fell from 1 to 0 and 68 to 0 days (p < 0.001), respectively. In contrast, discontinuers (47%) exhibited inferior outcomes and showed only a 29.9% reduction in admissions over 5 years. Patients were more likely to discontinue due to poor compliance and ineffectiveness and rarely due to tolerability issues. Apart from switching to ALAI from another LAI, there were no major clinical or demographic predictors of treatment continuation. Outcomes were consistent independent of diagnosis. Potential confounders however must not be overlooked, such as the exclusion of a large number of patients due to strict eligibility criteria as well as changes to healthcare policy over the study period. This is the first study to report 5-year hospitalisation and treatment persistence outcomes with ALAI. Its sustained use was associated with substantial reductions in hospital use, with 85% of completers requiring no further admissions, compared to 30% of discontinuers. These real-world findings support the long-term value of ALAI and may help address common barriers to LAI adoption in clinical decision-making.

Real-world effectiveness and tolerability of post solid organ transplant patients with CMV switching from valganciclovir treatment to maribavir: analysis using lab-linked claims data in the United States

ABSTRACT Background Antiviral (AV) treatment options (e.g. Valganciclovir, VGCV) for cytomegalovirus (CMV) infections present a challenging benefit-risk profile (e.g. bone-marrow suppression) and potentially increased resistance and refractoriness. Maribavir (MBV), a new AV treatment approved for refractory/resistant post-transplant CMV infections, demonstrated superior viral clearance in SOLSTICE trial. Research design and methods A retrospective lab-linked claims analysis of solid organ transplant (SOT) patients on VGCV (≥900 mg BID) treatment who newly switched to MBV (i.e. index date) between 1 December 2021 and31 December 2023. MBV treatment effectiveness (CMV viremia clearance/no treatment switch) and tolerability (e.g. leukopenia) during 3-months pre- and post-index was examined. Results Of the 1,247 post-SOT VGCV-treated patients, 81 switched to MBV; the mean age was 55 years, and 73% had kidney transplant. Among 33 with follow-up labs, 88% (n = 29) achieved viral clearance. Of the remaining 48 without follow-up labs, 60.4% (n = 29) did not switch to other AV treatments. The combined treatment effectiveness was 71.6%. Tolerability issues decreased after MBV initiation: with leukopenia, neutropenia, nausea, and diarrhea decreasing by 14.29%, 3.57%, 14.29%, and 17.86%, respectively. Conclusion MBV-treated patients had 10–15% lower tolerability issues; over 7 in 10 demonstrated treatment effectiveness in this real-world analysis. MBV’s favorable benefit-risk profile makes it a potentially valuable addition to the CMV treatment armamentarium. Clinical trial registration www.clinicaltrials.gov identifier is NCT02931539

Peran Content Creator sebagai Agen Bela Negara dalam Menangkal Disinformasi: Studi Kasus Konten Ferry Irwandi

Disinformation is one of the real threats to national stability in the digital era that needs to be addressed immediately. This study aims to analyze the role of content creators in countering disinformation in the digital era, focusing on Ferry Irwandi's content on social media. The method used is descriptive qualitative research with secondary data collection through content analysis of ten Ferry Irwandi videos. The results show that several of Ferry Irwandi’s contents feature five main thematic indicators: counter-narratives against disinformation, strengthening the narrative of national defense, digital and media literacy education, issues of tolerance and diversity, and social criticism based on national values. These findings demonstrate that defending the nation can be realized through creative, critical, and educational content, which becomes one of the key strategies in addressing the threat of disinformation in the digital space.

Implementasi Pendidikan Agama Berbasis Multikultural untuk Mengembangkan Sikap Toleransi Beragama Siswa di SD Negeri Ngasemlemahbang

Religious tolerance issues in multicultural elementary school environments remain a significant challenge, particularly in pluralistic societies like Indonesia, where disharmony may arise without early cultivation of mutual respect. This study aims to explore the implementation of multicultural-based religious education in fostering students’ attitudes of religious tolerance at SDN Ngasemlemahbang, a school characterized by religiously heterogeneous social settings. A qualitative descriptive approach was employed, with data collected through observation, interviews, and documentation involving the principal, Islamic and Christian religious teachers, and fifth- and sixth-grade students as research subjects. Data analysis proceeded through data condensation, presentation, and conclusion drawing. The findings reveal that multicultural-based religious education was implemented through segregated religious classes according to students’ faiths, habituation of religious activities, and interfaith interactions within the school environment. These strategies successfully enhanced students’ understanding and mutual respect across different religious backgrounds. In conclusion, a multicultural approach to religious education is effective in nurturing religious tolerance attitudes at the elementary school level. The implication is that this educational model can serve as a reference for other schools with similar diversity to create an inclusive, peaceful, and harmonious educational environment.

Abstract P4-07-26: CDK 4/6 inhibitor switching and associated dosing patterns in Swedish HR+/HER2- MBC patients

Abstract Background: The combination of CDK4/6 inhibitors (CDK4/6i) and endocrine therapy is a first-line treatment standard in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC). Switching between CDK4/6i may be used to manage side-effects prior to progression, and the postMONARCH study recently showed evidence on improving efficacy when sequencing CDK4/6i post progression. Limited evidence on real-world switching and associated dosing patterns within this class of drugs exist. This study investigated the frequency and timing of CDK4/6i switching and dosing before and after switch in a real-world setting using a nationwide Swedish cohort of MBC patients. Methods: This was a retrospective analysis utilizing the population-based Swedish Prescription Registry. The overall cohort included all patients with ≥ 1 dispensation of &amp;gt;1 of the available CDK4/6i (palbociclib, ribociclib and abemaciclib) from January 2017 – May 2024. Dosing before and after switch, overall frequency of CDK4/6i switching as well as time from the start of the first CDK4/6i to the subsequent were investigated. Only the first switch was considered. Information on treatment line of therapy and reason for switching was not available. Patient baseline characteristics and demographics were not available. Results: Out of 5781 patients with ≥ 1 dispensation of a CDK4/6i, 606 patients (11%) receiving &amp;gt;1 CDK 4/6i were analyzed. The most common switch was from ribociclib; 18% of 1756 patients who started with ribociclib changed to another CDK4/6i: 75% to palbociclib and 25% to abemaciclib. The second most common switch was from palbociclib; 8% of 2905 patients who started with palbociclib changed to another CDK4/6i: 55% to abemaciclib and 45% to ribociclib. There were 58 patients who switched from abemaciclib to another CDK4/6i, representing 5% of 1120 patients. Notably, this may also include patients in the adjuvant setting; 64% changed to palbociclib and 36% to ribociclib. Within 3 months of initiating CDK4/6i treatment, 201 patients out of the total 606 patients (33%) switched, with most changing from ribociclib; ribociclib-palbociclib (57%) and ribociclib-abemaciclib (15% patients). The remaining switches occurred 4-6 (27%), 7-9 (11%), or 10-12 (7%) months after treatment initiation. After more than a year on treatment, 136 patients (22%) switched CDK4/6i, with the majority changing from palbociclib; palbociclib-abemaciclib (37%) and palbociclib-ribociclib (35%). Prior to the switch, 343 patients (57%) were on full dose of the initial CDK4/6i treatment, and this share was highest for patients who switched within 0-3 months (71%), and lowest for patients who changed CDK4/6i after more than a year (40%). Half of the patients began the subsequent CDK4/6i treatment on the label dose, and this proportion was highest for patients with a change after more than a year (57%) and varied between 51% for patients switching between 0-3 months to 35% for patients switching between 9-12 months. Overall, 80% of patients started their initial CDK4/6i treatment on the full dose. Conclusion: Among Swedish patients who started treatment with a CDK4/6i, one in ten have switched to another CDK4/6i. The majority of patients switched to a subsequent CDK4/6i within 6 months of initiating their first CDK 4/6i. Most of these early switchers remained on full dose before the switch. The large proportion of early switchers may be related to tolerability issues. However, further investigation is needed to assess the clinical reasons and outcomes for such treatment changes. Despite the limitations of this real-world data analysis, these findings provide a new perspective around the trends related to switching and associated dosing in patients treated with CDK 4/6i. Citation Format: Daniel Nyqvist, Antonios Valachis, Henrik Lindman, Mate Szilcz, Maria Jakobsson. CDK 4/6 inhibitor switching and associated dosing patterns in Swedish HR+/HER2- MBC patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-07-26.

Spanning Pandemic Pandect – Caring, Compassion, and Crises Amidst COVID-19

David Carlgren's insider narrative documents in graphic details the lived experiences of his family and himself, and as importantly, presents the positive and negative experiences of a few colleagues in Wuhan, China during the pandemic. The author discusses issues of stress, tolerance, friendship, compassion and survival. With deep sensitivity David Carlgren explains: firstly, the coping and survival strategies adopted by his family. Secondly, a colleague's compassionate neighbours who deliberately intervened and ameliorated her situation. Thirdly, another colleague's stresses at school when he was forced to set up and take down, every day, the online teaching-learning technology, as well as to scan and upload the learning materials for a whole floor of classes. Fourthly was Carlgran's explicit description of the types and impacts of the stresses encountered by a third colleague.

0833 Long-Term Safety and Tolerability of Once-Nightly Sodium Oxybate: A Post Hoc Analysis from RESTORE

Abstract Introduction Once-nightly sodium oxybate (ON-SXB; LUMRYZ™) is an extended-release formulation of sodium oxybate that eliminates the second, middle-of-the-night dose required by immediate-release twice-nightly oxybate (TN-OXB) formulations. RESTORE (NCT04451668) was an open-label/switch study evaluating the long-term safety/tolerability of ON-SXB in people with narcolepsy. Methods Participants ≥16 years of age with narcolepsy who had completed the phase 3 REST-ON trial, were on stable-dose TN-OXB (switch participants), or were oxybate-naïve were eligible for RESTORE. Switch participants’ initial ON-SXB doses were equivalent/closest to their prior total nightly TN-OXB dose. After participants titrated their ON-SXB dose (±1.5 g/week; maximum, 9 g/night) with no tolerability issues for ≥3 months, participants entered the stable dosing period. Treatment-emergent adverse events (TEAEs) were recorded quarterly for switch participants in the safety population (all participants who received ≥1 dose of ON-SXB). Results A total of 130 switch participants were included in the safety population and received ON-SXB for a median (range) duration of 502.5 (8-1169) days during the &amp;gt;3-year study. Of these participants, 115 continued into the stable dosing period and were included in this analysis. Of the 115 who entered the stable dosing period, 73.9% (85/115) reported ≥1 TEAE. TEAEs reported by ≥3% of participants included COVID-19 (18.3%), nasopharyngitis (11.3%), nausea (10.4%), sinusitis (8.7%), fall (8.7%), headache (7.0%), enuresis (7.0%), cough (6.1%), upper respiratory tract infection (5.2%), urinary tract infection (5.2%), somnolence (4.3%), tremor (4.3%), vomiting (3.5%), dyspnea (3.5%), rash (3.5%), decreased appetite (3.5%), hypertension (3.5%), concussion (3.5%), and contusion (3.5%). Eight (7%) participants reported ≥1 serious TEAE (events, n=10); of these, 2 serious TEAEs were deemed related to ON-SXB (gastroesophageal reflux disease and cataplexy). Five participants (4.3%) experienced ≥1 TEAE that led to ON-SXB discontinuation (upper abdominal pain, fatigue, fall, dizziness, paresthesia, irritability, nightmare, and hypertension; n=1 [0.9%] each). Conclusion Reported AEs were consistent with the known AEs of oxybates. Only 4% of participants discontinued owing to a TEAE during the stable dosing period, underscoring the largely transient nature of AEs and the long-term tolerability of ON-SXB. Support (if any) Avadel Pharmaceuticals

Religious tolerance and national security in the context of the general theory of politics of Ukraine

The article proves that religious tolerance is a fundamental value of modern democratic society. It promotes the preservation of peace, ensures stability, and fosters mutual understanding between different national and ethno-cultural communities. It is emphasized that in the modern security environment, the issue of religious tolerance becomes relevant not only in interfaith relations but also for ensuring peace. It is substantiated that religious processes in Ukraine are closely connected with the security dimension of both individual states and the international community. It is noted that since gaining independence, Ukraine has been trying to develop its own model of national policy in thereligious sphere. This issue has become particularly acute in connection with military events. An effective model of interfaith and state-church relations is a strategically important issue of national security. It is shown that this issue is closely intertwined with the problem of self-identification of Ukrainians and influences the formation of national consciousness. Ukraine’s cooperation with European partners in this context should include experience exchange, development of joint projects and programs aimed at strengthening interreligious dialogue and preventing the emergence of new conflicts on religious grounds. Such cooperation will not only enhance the level of security but also create conditions for harmonious coexistence of various religious traditions, contributing to the formation of an open and tolerant society. The article concludes that the issue of religious tolerance is gaining a new level of significance not only in Ukraine but also globally. Large-scale military confrontations often have a pronounced religious component. Therefore, it is urgently necessary for Ukraine to develop an effective and stabilizing model of the security dimension taking the religious factor into account. Promising research in the field of general political theory will allow for a deeper understanding of the mechanisms for ensuring religious peace and stability both in Ukraine and in European countries. This is an integral part of democratic development and constructive international cooperation.

Xiao Yao San mitigates corticosterone stimulation-induced hippocampal neuronal damage by inhibiting GR phosphorylation and nuclear translocation via FKBP4 involvement

BackgroundCorticosterone stimulation has profound physiological and neurological effects on individuals, necessitating effective interventions to mitigate its impact. Current therapeutic approaches for corticosterone stimulation injury have limitations, including addiction and tolerance issues. In contrast, historical formulations such as Xiao Yao San, a traditional Chinese medicine formula, have shown promise in addressing changes in corticosterone stimulation-related neuroplasticity. This study aimed to explore the potential of Xiao Yao San in modulating the glucocorticoid receptor (GR) signaling pathway and its downstream effects on hippocampal neuroplasticity under corticosterone stimulation conditions.MethodsPrimary hippocampal neurons were cultured and exposed to corticosterone to establish a corticosterone stimulation model. Cellular viability, apoptosis, and protein expression were assessed via CCK-8 assays, flow cytometry, and immunoblotting, respectively. Interactions between FK506 binding protein 51 (FKBP51), GR, and p-GR were analyzed via coimmunoprecipitation and GST pull-down assays. The influence of FKBP4 on the competitive binding of GR was explored via similar techniques. The functional consequences of gene knockdown and overexpression were evaluated through cellular assays.ResultsXiao Yao San attenuated corticosterone-induced reductions in cell viability and apoptosis, counteracting the detrimental effects of corticosterone stimulation. It downregulated FKBP51 expression and suppressed GR phosphorylation and nuclear translocation. Additionally, it hindered the interaction between FKBP51 and GR/p-GR. FKBP4 overexpression rescued hippocampal neuron viability and protected against the GR phosphorylation and nuclear translocation induced by corticosterone.ConclusionXiao Yao San exhibited promising effects in ameliorating changes in corticosterone stimulation-induced neuroplasticity through the modulation of the GR signaling pathway. By inhibiting FKBP51-mediated GR phosphorylation and nuclear translocation, Xiao Yao San has potential as an alternative therapeutic strategy for corticosterone stimulation-related conditions. Further clinical investigations and mechanistic studies are warranted to validate its therapeutic efficacy and elucidate its mechanisms of action.

EC-Kad: An Efficient Data Redundancy Scheme for Cloud Storage

To address the issues of fault tolerance and retrieval efficiency in cloud storage space data, we propose an efficient cloud storage solution based on erasure codes. A cloud storage system model is designed to use erasure codes to distribute the encoded original data files across various nodes of the cloud storage system in a decentralized manner. The files are decoded by the receiver to complete data recovery and ensure high availability of the data files while optimizing redundant computing overhead during data storage, thereby improving the stability of encoding and decoding and reducing the bit error rate. Additionally, the Kademlia protocol is utilized to improve the retrieval efficiency of distributed disaster recovery storage data blocks. The proposed solution is tested on the Hadoop cloud storage platform, and the experimental results demonstrate that it not only maintains high availability but also enhances the efficiency of retrieving data files.

Abstract 1749: Discovery of MOMA-313, a potent and selective inhibitor of the Polθ DNA helicase domain for the treatment of HR-deficient tumors

Abstract Loss of homologous recombination (HR), a core DNA damage repair pathway, is common in many types of cancer that are caused by inactivating mutations in BRCA1, BRCA2 and functionally related proteins. HR-deficient tumors are widely treated with PARP inhibitors, but the duration of response and survival benefit is often limited by tolerability issues and by the emergence of clinical resistance mediated by secondary mutations that restore HR activity. MOMA-313 is a novel, potent and selective small molecule inhibitor of DNA polymerase theta (Polθ) in development with a PARP inhibitor to drive deeper and more durable responses in HR-deficient tumors. Polθ is a DNA repair enzyme composed of both a helicase and a polymerase domain that work in tandem to repair DSBs through a process called theta-mediated end-joining (TMEJ). Polθ functions as a back-up DNA repair pathway in most contexts, and genetic ablation of Polθ is well-tolerated in mouse models and in HR-proficient cell lines. However, when HR is disabled, cells rely heavily on Polθ activity for DSB repair. Loss of Polθ activity may also prevent the emergence of clinical PARP inhibitor resistance caused by BRCA reversion mutations which have been linked to Polθ DNA repair activity. MOMA-313 is an inhibitor of the Polθ helicase domain that inhibits cellular TMEJ activity in vitro and in vivo with single-digit nM potency. MOMA-313 synergizes with PARP inhibitors against HR-deficient cell lines in vitro, with no combination impact on HR-proficient cells. Low doses of MOMA-313 drive the regression of HR-deficient tumor xenografts when combined with the PARP inhibitor olaparib, including in models with limited response to olaparib alone. A PK/PD/efficacy relationship directly links exposures required for tumor regressions to target inhibition, as determined by measuring TMEJ inhibition within tumor xenografts. Mechanistically, cryo-EM studies demonstrate MOMA-313 binds to the DNA channel, preventing DNA translocation and synapse formation between opposing ends of the broken DNA. By inhibiting the first of the two sequential Polθ DNA repair activities, MOMA-313 likely prevents the engagement of either Polθ functional domain. MOMA-313 has been optimized to achieve high target coverage at a low human dose, a strong safety profile, and broad combinability especially with PARP inhibitors, where mechanistic synergy may drive deeper responses and prevent clinical resistance in HR-deficient tumors. Clinical evaluation of MOMA-313 is ongoing (NCT06545942), with monotherapy and PARP inhibitor combination arms. Citation Format: Jordan A. Krall, Michael Reutershan, Vinny Motwani, Kelly McGlynn, Yonghong Bai, Christopher Quinn, Manaswni Dhingra, Cen Gao, David Waller, Salah Nabhan, Marc Ballas, Timothy Guzi, Peter Hammerman, Erica Evans. Discovery of MOMA-313, a potent and selective inhibitor of the Polθ DNA helicase domain for the treatment of HR-deficient tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1749.

Ketoprofen Lysine Salt vs. Ketoprofen Acid: Assessing the Evidence for Enhanced Safety and Efficacy.

Endoscopic investigations reveal that a significant majority of individuals taking NSAIDs exhibit acute hemorrhages and mucosal erosions within the gastroduodenal lining. Ketoprofen acid (KA) is a potent NSAID with established efficacy and cardiovascular tolerability, but its gastric tolerability is a recognized limitation. To mitigate this, ketoprofen lysine salt (KLS) was developed. This review evaluates the pharmacological advantages of KLS over KA. While both KA and KLS maintain similar potency, KLS offers distinct advantages. Firstly, KLS demonstrates superior gastrointestinal protection through enhanced antioxidant properties and upregulation of mucosal defenses, as evidenced by both in vitro and in vivo studies. Secondly, KLS exhibits significantly faster absorption, leading to a more rapid onset of analgesic effects; this is attributed to its increased solubility and faster achievement of therapeutic concentrations. In essence, KLS addresses the gastric tolerability issues of KA while providing a quicker onset of action, making it a valuable alternative for patients requiring NSAID therapy, particularly those with gastric sensitivities or in need of rapid pain relief.

Conflict Tolerance in The City of Students (Case Study of Church Construction Rejection in Cilegon City)

Conflict tolerance that occurred in Cilegon City, Banten, related to the church construction rejection in the Cilegon city, known as the "city of students" facing challenges related to the religious tolerance issue. This journal aims to analyze the roots of conflict, dynamics, and socio-political rejection implications. The factors that cause the rejection as well as the dynamics of conflict tolerance in Cilegon by using the historical context of the Charter of Medina at the time of the Prophet Muhammad. The results showed that construction rejection of churches in Cilegon was caused by various factors, such as religious sentiment, identity politics, and distrust of the government. The dynamics of conflict tolerance in Cilegon is also influenced by history and complex local context. This article concludes that efforts to build tolerance in Cilegon require a comprehensive approach, involving various stakeholders, and based on universal human values as reflected in the Medina Charter.

Multicultural Islamic Education as Strategy for Strengthening Social Cohesion in Islamic School

Issues of social cohesion and interfaith tolerance are crucial in the context of diverse societies, including Bali, Indonesia, and Southern Thailand, which have experienced conflicts related to religious and cultural differences. This study aims to explore the role of multicultural Islamic education in strengthening social cohesion at Bali Bina Insani Islamic School (SI-BBI) and Phatnawitya School (PS). Utilizing a qualitative case study approach, this research employs in-depth interviews, participant observation, and documentation with school principals and teachers at both schools as primary data sources, which are then analyzed using descriptive-qualitative methods. The findings reveal that multicultural Islamic education at SI-BBI is implemented through the integration of local cultural values into the curriculum, such as the use of the Balinese language and the recruitment of Hindu teachers, as a form of acculturation that fosters social cohesion among the Muslim minority and Hindu majority in Bali. Meanwhile, at PS, multicultural Islamic education is applied with the inclusive principle of rahmatan lil alamin, incorporating cross-cultural learning and reinforcing tolerance values for students in the Muslim-majority but locally cultural region of Southern Thailand. These findings expand the understanding of Social Identity Theory from Henri Tajfel and John Turner, by demonstrating that multicultural education can reduce identity conflicts and strengthen social integration through learning that respects diversity. The implications of this research emphasize the need for educational policies that are friendly to religious and cultural diversity, which support the integration of multicultural values ​​in the education system in areas with potential for conflict. The multicultural Islamic education models in these two schools offer strategic frameworks for application in contexts of cultural and religious diversity, aiming to create sustainable social cohesion.

Considering Long-Acting Synthetic Cannabidiol for Chronic Pain: A Narrative Review.

Chronic pain is prevalent and challenging to treat. Cannabinoids, in particular cannabidiol (CBD), have been evaluated as analgesics without the issues of tolerance or dependence. Side effects tend to be mild and infrequent. These products have multiple routes of administration and composition, and some are available over the counter, allowing pain patients to self-medicate. Most self-medicated CBD are plant-derived extracts administered as either oils, pills, or by inhalation. During the early 1960s, CBD was chemically synthesized for the first time, but it was not yet approved for medical use; synthetic CBD has been and continues to be studied in clinical trials for numerous indications, including chronic pain, neuropathic pain, and pain in cancer. However, studies are often small, populations heterogeneous, and some results are equivocal. Research is lively, with over 60 studies reported on ClinicalTrials.gov. Multimodal CBD therapy may hold promise, particularly in combination with palmitoylethanolamide. Greater patient education and training for physicians and other healthcare providers are needed along with more comprehensive studies. Considering the problem of chronic pain, further intensive study of synthetic CBD for pain control is warranted to meet this unmet clinical need. This is particularly important in the context of long-lasting administration methods that enable easy dosing and support long-term use for patients dealing with persistent and often debilitating symptoms.

Randomized Phase IIa Trial of Purified Candida Antigen for Common Warts: Evaluating the Safety and Efficacy Across Multiple Dosing Regimens

IntroductionNon-standardized Candida albicans antigens are commonly used for the treatment of common warts (verruca vulgaris); however, clinical studies thus far have not determined optimal dosing. This study assessed three dosing schemes using Candin®, a standardized purified Candida antigen (PCA), for the treatment of common warts.MethodsThis placebo-controlled, randomized phase IIa clinical trial included participants that had 3 to 20 injectable common warts on prespecified anatomical regions. PCA was administered intralesionally for up to 10 injections every 2 weeks, with adjustments to every 3 weeks for local tolerance issues. Three dosing regimens were evaluated: 0.3 or 0.5 mL into a single wart (cohorts 1 and 2, respectively), or 0.3 mL into up to four warts (cohort 3). Total injection volumes in cohorts 2 and 3 were larger than the typical off-label use of C. albicans. The primary outcome was complete resolution of injected warts, while secondary outcomes included safety, tolerability, and the clearance of untreated common warts.ResultsThe incidence of clearance of the primary injected wart in placebo participants was 41.9%, compared to 65.9% (relative risk [RR] 1.57; 95% confidence interval [CI] 1.02, 2.42; P = 0.03) in cohort 1, 79.5% (RR 1.89; 95% CI 1.27, 2.82; P = 0.0007) in cohort 2, and 72.5% (RR 1.74; 95% CI 1.19, 2.50; P = 0.005) in cohort 3, and treatment was well tolerated. Injection of 0.5 mL PCA into a single wart also resulted in a significantly higher rate of clearance of untreated common warts compared to placebo (RR 3.2, 95% CI 1.2, 8.0, P = 0.001).ConclusionAll three dosing regimens of PCA were safe, well tolerated, and resulted in significantly greater clearance of the primary treated wart(s) compared to placebo, but only 0.5 mL injected into a single wart was significantly better than placebo at clearing untreated warts. Typically, a volume of 0.3 mL C. albicans antigen is injected into a single wart; however, these results suggest that a larger volume of 0.5 mL may have greater benefit for patients. A phase III clinical trial is currently underway to confirm these findings.Trial RegistrationClinicalTrials.gov NCT02393417.

From TOLERANCE IS BUSINESS to TOLERANCE IS CLOTHING

So far, religious tolerance in the mass media has never been studied using metaphors in a cognitive linguistic approach. In fact, through conceptual metaphors, the framing of the mass media will emerge on the issue of religious tolerance. This qualitative descriptive research collects data on news and articles about religious tolerance in online Islamic mass media during the period 2018–2023. Data were analyzed using metaphor identification procedure, conceptual metaphor theory, and mixed metaphor. The results of the study show that there are 9 source domains, namely 1) TOLERANCE IS CLOTHES, (2) TOLERANCE IS SPACES/BUILDINGS, (3) TOLERANCE IS HUMANS, (4) TOLERANCE IS THE BODY, (5) TOLERANCE IS PLANTS, and (6) TOLERANCE IS ARE THINGS, (7) TOLERANCE IS A BUSINESS COMMODITY, (8) TOLERANCE IS WAR, and (9) TOLERANCE IS A VEHICLE. In general, the metaphor of tolerance in online Islamic mass media is classified into three tones, that is positive tones, negative tones, and neutral tones. Online Islamic mass media that have a positive tone are NU Online and Alif.id, mass media with a mixed tone (positive-neutral) is Suara Muhammadiyah and (positive-neutral-negative) is Hidayatullah.com, and mass media with a positive tone negative are Portal Islam, Suara Islam, VOA Islam, and Era Muslim.

Ecological Momentary Assessment of emotional dysregulation and outbursts among youth with ADHD: a feasibility study of a biomarker-driven predictive algorithm in the special education pre-K and early childhood classroom settings.

Attention Deficit Hyperactivity Disorder (ADHD) among children younger than 6 years is quite impairing, nearly half these youth with ADHD experience school exclusion from mainstream preschool classes due to related emotional and behavioral outbursts. While a range of behavior rating scales and subjective measures are used to assess these youth, objective methods of assessment and prediction derived from technology have potential to improve therapeutic and academic interventions outcomes for these youths. We hypothesized that biometric sensors would provide objective, highly sensitive and specific information regarding the physiological status of children prior to an impulsive outburst and could be feasibly implemented using a wearable device in the special education classroom. We recruited two whole classrooms (N = 5 youth in the pre-K class and N = 5 youth from the first grade) of a specialized therapeutic day-school for youth with ADHD and other psychiatric and developmental disorders to examine feasibility of obtaining continuous physiological data associated with behavioral and emotional outbursts through smartwatch use. Children wore a sensor watch during their daily classroom activities for two weeks and trained observers collected data using behavioral logs. Using Ecological Momentary Assessment methodology, to examine correlations between objective sensor data and observer observation. Data collected from parents regarding prior night's sleep was also examined. All participants completed the study. With a few tolerability or palatability issues. Associations were found between physiological and behavioral/questionnaire data. The methodology holds promise for reliably measuring behavioral and emotional outbursts in young children. This is the first study to use a bio-marker device in vivo among severely dysregulated pre-school aged youth throughout a full school day. This study established the feasibility of utilizing sensor derived physiological data as an objective biomarker of ADHD within the special education therapeutic classroom. Further research with larger samples is required to build a more robust and personalized AI predictive model.