Benchmarking predictive methods for small-angle X-ray scattering from atomic coordinates of proteins using maximum likelihood consensus data.

Stimulated by informal conversations at the XVII International Small Angle Scattering (SAS) conference (Traverse City, 2017), an international team of experts undertook a round-robin exercise to produce a large dataset from proteins under standard solution conditions. These data were used to generate consensus SAS profiles for xylose isomerase, urate oxidase, xylanase, lysozyme and ribonuclease A. Here, we apply a new protocol using maximum likelihood with a larger number of the contributed datasets to generate improved consensus profiles. We investigate the fits of these profiles to predicted profiles from atomic coordinates that incorporate different models to account for the contribution to the scattering of water molecules of hydration surrounding proteins in solution. Programs using an implicit, shell-type hydration layer generally optimize fits to experimental data with the aid of two parameters that adjust the volume of the bulk solvent excluded by the protein and the contrast of the hydration layer. For these models, we found the error-weighted residual differences between the model and the experiment generally reflected the subsidiary maxima and minima in the consensus profiles that are determined by the size of the protein plus the hydration layer. By comparison, all-atom solute and solvent molecular dynamics (MD) simulations are without the benefit of adjustable parameters and, nonetheless, they yielded at least equally good fits with residual differences that are less reflective of the structure in the consensus profile. Further, where MD simulations accounted for the precise solvent composition of the experiment, specifically the inclusion of ions, the modelled radius of gyration values were significantly closer to the experiment. The power of adjustable parameters to mask real differences between a model and the structure present in solution is demonstrated by the results for the conformationally dynamic ribonuclease A and calculations with pseudo-experimental data. This study shows that, while methods invoking an implicit hydration layer have the unequivocal advantage of speed, care is needed to understand the influence of the adjustable parameters. All-atom solute and solvent MD simulations are slower but are less susceptible to false positives, and can account for thermal fluctuations in atomic positions, and more accurately represent the water molecules of hydration that contribute to the scattering profile.

Publicly Available Anatomic Total Shoulder Arthroplasty Rehabilitation Protocols Show High Variability and Frequent Divergence from the 2020 ASSET Recommendations.

Background: In 2020, the American Society of Shoulder and Elbow Therapists (ASSET) published an evidence-based consensus statement outlining postoperative rehabilitation guidelines following anatomic total shoulder arthroplasty (TSA). Purpose: The purpose of this study was to (1) quantify the variability in online anatomic TSA rehabilitation protocols, and (2) assess their congruence with the ASSET consensus guidelines. Methods: This study was a cross-sectional investigation of publicly available, online rehabilitation protocols for anatomic TSA. A web-based search was conducted in April 2022 of publicly available rehabilitation protocols for TSA. Each collected protocol was independently reviewed by two authors to identify recommendations regarding immobilization, initiation, and progression of passive (PROM) and active range of motion (AROM), as well as the initiation and progression of strengthening and post-operative exercises and activities. The time to initiation of various components of rehabilitation was recorded as the time at which the activity or motion threshold was permitted by the protocol. Comparisons between ASSET start dates and mean start dates from included protocols were performed. Results: Of the 191 academic institutions included, 46 (24.08%) had publicly available protocols online, and a total of 91 unique protocols were included in the final analysis. There were large variations seen among included protocols for the duration and type of immobilization post-operatively, as well as for the initiation of early stretching, PROM, AROM, resistance exercises, and return to sport. Of the 37 recommendations reported by both the ASSET and included protocols, 31 (83.78%) were found to be significantly different between groups (p\<0.05). Conclusion: Considerable variability was found among online post-operative protocols for TSA with substantial deviation from the ASSET guidelines. These findings highlight the lack of standardization in rehabilitation protocols following anatomic TSA. Level of Evidence: 3b.

Management from a multidisciplinary perspective of phlebitis related to peripheral venous catheter insertion: An international Delphi study.

AIM: To determine the consensus and importance of care practices related to the management of peripheral venous catheter (PVC)-related phlebitis in hospitalized patients through the views of experts from different disciplines. BACKGROUND: PVCs are commonly used in hospitals but are associated with complications such as phlebitis. Their management differs widely, and studies are heterogeneous. DESIGN: Delphi method. METHODS: Four stages: problem area (with Web of Science bibliometric review in July 2022), panel members, two Delphi rounds and closing criteria. In the Delphi survey, experts answered an online questionnaire based on assessment, treatment and follow-up dimensions (September 2022-February 2023). Statistical analyses were conducted of frequencies, percentages, measures of central tendency and levels of dispersion (QD). A space for comments was created, and a thematic analysis conducted of them. RESULTS: Eighteen experts (nurses, doctors and pharmacists) participated in the Delphi rounds. Forty-five activities were identified: 19 in assessment, 15 in treatment and 11 in follow-up. A high consensus level (QD ≤ 0.6) was found in five activities (11.12%), moderate level (0.6 < QD < 1.0) in 19 (42.22%) and low level (QD > 1.0) in 21 (46.66%). Seven themes were determined (patient perspective, lack of consensus, low evidence-based practices, stage-based treatments, prevention activities, high variability in practice and specialist teams and interdisciplinary work). CONCLUSION: The importance of systematic assessment scales is highlighted together with consensus on signs and symptoms (pain, redness, inflammation, palpable cord and induration). Treatment according to severity and daily visual recording and monitoring are emphasized along with the need for patient participation and healthcare literacy. A high level of consensus was obtained in 11% of the activities, showing the large variability of criteria and interventions for phlebitis management. Highlighted needs include working in a team, the use of specialist teams and promoting evidence- and prevention-based activities. RELEVANCE TO CLINICAL PRACTICE: Clinical variability is noted and, therefore, the importance of consensus on standardized care for PVC phlebitis and evidence-based practice. REPORTING METHOD: Delphi studies (CREDES). PATIENT OR PUBLIC CONTRIBUTION: Experts contribution.

Advancing lung adenocarcinoma prognosis and immunotherapy prediction with a multi-omics consensus machine learning approach.

Lung adenocarcinoma (LUAD) is a tumour characterized by high tumour heterogeneity. Although there are numerous prognostic and immunotherapeutic options available for LUAD, there is a dearth of precise, individualized treatment plans. We integrated mRNA, lncRNA, microRNA, methylation and mutation data from the TCGA database for LUAD. Utilizing ten clustering algorithms, we identified stable multi-omics consensus clusters (MOCs). These data were then amalgamated with ten machine learning approaches to develop a robust model capable of reliably identifying patient prognosis and predicting immunotherapy outcomes. Through ten clustering algorithms, two prognostically relevant MOCs were identified, with MOC2 showing more favourable outcomes. We subsequently constructed a MOCs-associated machine learning model (MOCM) based on eight MOCs-specific hub genes. Patients characterized by a lower MOCM score exhibited better overall survival and responses to immunotherapy. These findings were consistent across multiple datasets, and compared to many previously published LUAD biomarkers, our MOCM score demonstrated superior predictive performance. Notably, the low MOCM group was more inclined towards 'hot' tumours, characterized by higher levels of immune cell infiltration. Intriguingly, a significant positive correlation between GJB3 and the MOCM score (R = 0.77, p < 0.01) was discovered. Further experiments confirmed that GJB3 significantly enhances LUAD proliferation, invasion and migration, indicating its potential as a key target for LUAD treatment. Our developed MOCM score accurately predicts the prognosis of LUAD patients and identifies potential beneficiaries of immunotherapy, offering broad clinical applicability.

Timing decisions as the next frontier for collective intelligence.

The past decade has witnessed a growing interest in collective decision making, particularly the idea that groups can make more accurate decisions compared with individuals. However, nearly all research to date has focused on spatial decisions (e.g., food patches). Here, we highlight the equally important, but severely understudied, realm of temporal collective decision making (i.e., decisions about when to perform an action). We illustrate differences between temporal and spatial decisions, including the irreversibility of time, cost asymmetries, the speed-accuracy tradeoff, and game theoretic dynamics. Given these fundamental differences, temporal collective decision making likely requires different mechanisms to generate collective intelligence. Research focused on temporal decisions should lead to an expanded understanding of the adaptiveness and constraints of living in groups.

Identification of disease phenotypes in acetylcholine receptor-antibody myasthenia gravis using proteomics-based consensus clustering.

BACKGROUND: The clinical heterogeneity of myasthenia gravis (MG), an autoimmune disease defined by antibodies (Ab) directed against the postsynaptic membrane, constitutes a challenge for patient stratification and treatment decision making. Novel strategies are needed to classify patients based on their biological phenotypes aiming to improve patient selection and treatment outcomes. METHODS: For this purpose, we assessed the serum proteome of a cohort of 140 patients with anti-acetylcholine receptor-Ab-positive MG and utilised consensus clustering as an unsupervised tool to assign patients to biological profiles. For in-depth analysis, we used immunogenomic sequencing to study the B cell repertoire of a subgroup of patients and an in vitro assay using primary human muscle cells to interrogate serum-induced complement formation. FINDINGS: This strategy identified four distinct patient phenotypes based on their proteomic patterns in their serum. Notably, one patient phenotype, here named PS3, was characterised by high disease severity and complement activation as defining features. Assessing a subgroup of patients, hyperexpanded antibody clones were present in the B cell repertoire of the PS3 group and effectively activated complement as compared to other patients. In line with their disease phenotype, PS3 patients were more likely to benefit from complement-inhibiting therapies. These findings were validated in a prospective cohort of 18 patients using a cell-based assay. INTERPRETATION: Collectively, this study suggests proteomics-based clustering as a gateway to assign patients to a biological signature likely to benefit from complement inhibition and provides a stratification strategy for clinical practice. FUNDING: CN and CBS were supported by the Forschungskommission of the Medical Faculty of the Heinrich Heine University Düsseldorf. CN was supported by the Else Kröner-Fresenius-Stiftung (EKEA.38). CBS was supported by the Deutsche Forschungsgemeinschaft (DFG-German Research Foundation) with a Walter Benjamin fellowship (project 539363086). The project was supported by the Ministry of Culture and Science of North Rhine-Westphalia (MODS, "Profilbildung 2020" [grant no. PROFILNRW-2020-107-A]).

Medicinal plants traditionally used in health care practices by inhabitants of Paddar region of Jammu and Kashmir, India.

ETHNOPHARMACOLOGICAL RELEVANCE: The present study is the first quantitative assessment of ethno-medicinal plants of Paddar region of Jammu and Kashmir. AIM OF THE STUDY: The study aimed to document the relative importance of medicinal plants used in human ailments by the villagers in the Paddar region of Jammu and Kashmir, India. MATERIAL AND METHODS: Data were collected from 132 informants (72 male and 60 female) through semi structured interviews and group discussions. Use report (UR) and Informant consensus factor (ICF) were employed to quantitatively examine the data. RESULTS: The inhabitants of Paddar reported the use of 98 plants species of 55 families to treat 63 ailments. Rosaceae (10 spp.) was the most frequently used family in the study area. Herbs were dominantly (66 spp., 50%) utilized in herbal preparation and leaves the mostly used plant parts (25%). The highest informant consensus factor (ICF=0.96) was obtained for parasitic problems. Important new uses for species stated by informants to treat human diseases were; Viburnum grandiflorum Wall. ex DC., Sium latijugum C.B.Clarke, Corylus jacquemontii Decne., Capsella bursa-pastoris (L.) Medik., Cannabis sativa L., Taraxacum campylodes G.E.Haglund, Euphorbia helioscopia L., Juglans regia L., Cotoneaster acuminatus Lindl., Ficus palmata Forssk., Plantago lanceolata L., and Eleusine coracana (L.) Gaertn. CONCLUSIONS: The current study contributes towards the preservation of indigenous plants' based knowledge. Although the therapeutic value of most of the preferred medicinal plants has already been validated, some medicinal plants lack proper scientific validation. We recommend further phytochemical investigations and pharmacological validations of Viburnum grandiflorum, C. jacquemontii, F. palmata, Viola pilosa, Cotoneaster acuminatus, Eleucine coracana, Sium latijugum, Aquilegia pubiflora, Euphorbia helioscopia, Plantago lanceolata and Pinus gerardiana.

Platelet-rich plasma injections for the management of knee osteoarthritis: The ESSKA-ICRS consensus. Recommendations using the RAND/UCLA appropriateness method for different clinical scenarios.

PURPOSE: The aim of this consensus was to develop evidence- and expert-based patient-focused recommendations on the appropriateness of intra-articular platelet-rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). METHODS: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. RESULTS: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50-65/66-80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren-Lawrence/KL 0-I/II-III/IV), and joint effusion (dry knee, minor-mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0-III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). CONCLUSION: This ESSKA-ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0-III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. LEVEL OF EVIDENCE: Level I.

Clinical practice recommendations for management of Diabetes Mellitus in Arab region: An expert consensus statement from Arab Diabetes Forum (ADF).

Prevalence of diabetes in Arab region has significantly increased, resulting in a significant economic burden on healthcare systems. This surge can be attributed to obesity, rapid urbanization, changing dietary habits, and sedentary lifestyles. The Arab Diabetes Forum (ADF) has established localized recommendations to tackle the region's rising diabetes prevalence. The recommendations, which incorporate worldwide best practices, seek to enhance the quality of treatment for people with diabetes by raising knowledge and adherence among healthcare providers. The guidelines include comprehensive recommendations for screening, diagnosing, and treating type 1 and type 2 diabetes in children and adults for better overall health results.

Development of a research agenda for medical grade footwear in the Netherlands: A multidisciplinary multiphase project to determine the key research questions to advance scientific knowledge in the field.

BACKGROUND: The field of medical grade footwear is dynamic. Originally, a field where individual knowledge, expertise and skills determined the footwear and its outcomes, now becoming a more evidence-based and data-driven field with protocols and systems in place to create appropriate footwear. However, scientific evidence concerning medical grade footwear is still limited. Evidently, all stakeholders, from patients to pedorthists to rehabilitation physicians, will profit from a larger evidence-base in this field. A widely supported research agenda is an essential first step to advance and facilitate new knowledge. METHODS: We formed a multidisciplinary team and followed the methodology from Dutch medical societies for the development of a research agenda on medical grade footwear. This consisted of seven steps: (1) inventory of relevant questions with users and professionals; (2) analyses of responses; (3) analyses of existing knowledge and evidence; (4) formulating research questions; (5) prioritising research questions by users and professionals; (6) finalising the research agenda and (7) implementing the research agenda. RESULTS: In phase 1, 109 participants completed a survey, including 50% pedorthists, 6% rehabilitation physicians and 3% users. Participants provided 228 potential research questions. In phases 2-4, these were condensed to 65 research questions. In phase 5, 152 participants prioritised these 65 research questions, including 50% pedorthists, 13% rehabilitation physicians and 9% users. In phase 6, the final research agenda was created, with 26 research questions, categorised based on the International Classification of Functioning Disability and Health 'process description assistive devices'. In phase 7, an implementation meeting was held with over 50 stakeholders (including users and professionals), resulting in seven applications for research projects based on one or more research questions from the research agenda. CONCLUSIONS: This research agenda structures and guides knowledge development within the field of medical grade footwear in the Netherlands and elsewhere. We expect that this will help to stimulate the field to tackle the research questions prioritised and with that to advance scientific knowledge in this field.

Major Trauma Triage Tool Study (MATTS) expert consensus-derived injury assessment tool.

Introduction: Major trauma centre (MTC) care has been associated with improved outcomes for injured patients. English ambulance services and trauma networks currently use a range of triage tools to select patients for bypass to MTCs. A standardised national triage tool may improve triage accuracy, cost-effectiveness and the reproducibility of decision-making. Methods: We conducted an expert consensus process to derive and develop a major trauma triage tool for use in English trauma networks. A web-based Delphi survey was conducted to identify and confirm candidate triage tool predictors of major trauma. Facilitated roundtable consensus meetings were convened to confirm the proposed triage tool's purpose, target diagnostic threshold, scope, intended population and structure, as well as the individual triage tool predictors and cut points. Public and patient involvement (PPI) focus groups were held to ensure triage tool acceptability to service users. Results: The Delphi survey reached consensus on nine triage variables in two domains, from 109 candidate variables after three rounds. Following a review of the relevant evidence during the consensus meetings, iterative rounds of discussion achieved consensus on the following aspects of the triage tool: reference standard, scope, target diagnostic accuracy and intended population. A three-step tool comprising physiology, anatomical injury and clinical judgement domains, with triage variables assessed in parallel, was recommended. The triage tool was received favourably by PPI focus groups. Conclusions: This paper presents a new expert consensus derived major trauma triage tool with defined purpose, scope, intended population, structure, constituent variables, variable definitions and thresholds. Prospective evaluation is required to determine clinical and cost-effectiveness, acceptability and usability.

Blockchain technology and raft consensus for secure physician prescriptions and improved diagnoses in electronic healthcare systems.

With electronic healthcare systems undergoing rapid change, optimizing the crucial process of recording physician prescriptions is a task with major implications for patient care. The power of blockchain technology and the precision of the Raft consensus algorithm are combined in this article to create a revolutionary solution for this problem. In addition to addressing these issues, the proposed framework, by focusing on the challenges associated with physician prescriptions, is a breakthrough in a new era of security and dependability for the healthcare sector. The Raft algorithm is a cornerstone that improves the diagnostic decision-making process, increases confidence in patients, and sets a new standard for robust healthcare systems. In the proposed consensus algorithm, a weighted sum of two influencing factors including the physician acceptability and inter-physicians' reliability is used for selecting the participating physicians. An investigation is conducted to see how well the Raft algorithm performs in overcoming prescription-related roadblocks that support a compelling argument for improved patient care. Apart from its technological benefits, the proposed approach seeks to revolutionize the healthcare system by fostering trust between patients and providers. Raft's ability to communicate presents the proposed solution as an effective way to deal with healthcare issues and ensure security.

Controversies in prostate cancer management: Consensus recommendations from experts in northern Spain.

In recent years, various aspects of prostate cancer (PC) management have undergone significant changes, including the implementation of therapeutic strategies such as the use of new hormonal agents like abiraterone, apalutamide, enzalutamide or darolutamide and the incorporation of next generation imaging techniques (NGI). However, the evidence regarding the role of NGI and the therapeutic decision-making based on their findings is not solid. Following the methodology of the Advanced Prostate Cancer Consensus Conference (APCCC), a multidisciplinary expert consensus was developed to address controversial questions concerning the use of NGI and clinical management in four priority scenarios: localized PC, PC after radical prostatectomy, PC after radiotherapy with curative intent, and metastatic hormone-sensitive PC. This consensus represents the opinions of medical oncology, radiation oncology and urology physicians and provides useful recommendations for clinical practice.

Clinical Practice Recommendations for Hematopoietic Cell Transplantation and Cellular Therapies in Follicular Lymphoma: A Collaborative Effort on behalf of The American Society of Transplantation and Cellular Therapy and the European Society of Blood and Marrow Transplantation.

Follicular lymphoma (FL) is the most common indolent B-cell non-Hodgkin lymphoma (NHL), accounting for nearly one-third of all NHL. The therapeutic landscape for patients with FL has significantly expanded over the past decade, but the disease continues to be considered incurable. Hematopoietic cell transplantation (HCT) is potentially curative in some cases. Recently, the emergence of chimeric antigen receptor T-cell therapy (CAR-T) for patients with relapsed/refractory (R/R) FL has yielded impressive response rates and long-term remissions, but definitive statement on the curative potential of CAR-T is currently not possible due to limited patient numbers and relatively short follow up. A consensus on the contemporary role, optimal timing, and sequencing of HCT (autologous or allogeneic) and cellular therapies in FL is needed. As a result, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines endorsed this effort to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 15 consensus statements/recommendations. Of note, the use of bispecific antibodies in R/R FL was not in the scope of this project. Key statements/recommendations are as follows: 1) Autologous HCT is recommended as an option for consolidation therapy in patients with progression of untransformed disease within 24 months of front line chemoimmunotherapy and upon achieving a complete (CR) or partial response (PR) to salvage second line therapies; 2) CAR-T is considered as a treatment option for patients who did not achieve CR or PR after second or subsequent lines of therapies; 3) Allogeneic HCT is considered as consolidative treatment in relapsed FL patients with chemosensitive disease who have received 3 or more lines of systemic therapy and are the following clinical scenarios: post CAR-T failure; lack of access to CAR-T or have therapy related myeloid neoplasm. These clinical practice recommendations will help guide clinicians managing patients with FL.

Improvements in the Management of Patients With Generalized Pustular Psoriasis in Spain: Recommendations From a Group of Experts. / Mejoras en la atención al paciente con psoriasis pustulosa generalizada en España: recomendaciones de un grupo de expertos.

This consensus document analyzed the management and emotional journey of patients with GPP (generalized pustular psoriasis), and the desirable course of the disease while detecting critical points and translating them into needs and recommendations. This project was conducted in 3 phases with participation from an advisory committee (n = 8), an expert panel (n = 15) and patients with GPP (n = 6). The patients' disease progression was heterogeneous due to disease variations, different health care models implemented and available resources, and the lack of diagnostic and treatment guidelines. A total of 45 different recommendations have been made to optimize management and address the emotional component of these patients. Five of them stand out for their impact and viability. Therefore, a roadmap of priorities has been made generally available to improve the management of patients with GPP.

Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne. / Consenso Iberia sobre estrategias de prevención y manejo de la irritación por retinoides tópicos en acné localizado en cara y tronco.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥ 85% agreement in 22 recommendations and ≥ 70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

A consensus-based electronic medical record template for pediatric morphea patient visits.

Morphea, also known as localized scleroderma, is an inflammatory sclerosing disorder of uncertain pathogenesis that affects the skin and underlying tissues. In the pediatric population, the disease often runs a chronic course with a high risk for irreversible sequelae; as such, patients often require long-term monitoring. The objective of this study is to develop a multi-center, consensus-based electronic medical record template for pediatric morphea patient visits using a modified Delphi method of iterative surveys. By facilitating consistent data collection and interpretation across medical centers and patient populations, this template may improve patient care for pediatric patients with morphea.

Evidence-based expert consensus on clinical management of safety of Bruton's tyrosine kinase inhibitors (2024).

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment. A multidisciplinary consensus working group was established, comprising 35 members from the fields of hematology, cardiovascular disease, cardio-oncology, clinical pharmacy, and evidence-based medicine. This evidence-based expert consensus was formulated using an evidence-based approach and the Delphi method. The Joanna Briggs Institute Critical Appraisal (JBI) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach were used to rate the quality of evidence and grade the strength of recommendations, respectively. This consensus provides practical recommendations for BTKis medication based on nine aspects within three domains, including the management of common adverse drug events such as bleeding, cardiovascular events, and hematological toxicity, as well as the management of drug-drug interactions and guidance for special populations. This multidisciplinary expert consensus could contribute to promoting a multi-dimensional, comprehensive and standardized management of BTKis.

Signature identification based on immunogenic cell death-related lncRNAs to predict the prognosis and immune activity of patients with endometrial carcinoma.

Background: Endometrial carcinoma (EC) is one of the most prevalent gynecologic malignancies and requires further classification for treatment and prognosis. Long non-coding RNAs (lncRNAs) and immunogenic cell death (ICD) play a critical role in tumor progression. Nevertheless, the role of lncRNAs in ICD in EC remains unclear. This study aimed to explore the role of ICD related-lncRNAs in EC via bioinformatics and establish a prognostic risk model based on the ICD-related lncRNAs. We also explored immune infiltration and immune cell function across prognostic groups and made treatment recommendations. Methods: A total of 552 EC samples and clinical data of 548 EC patients were extracted from The Cancer Genome Atlas (TCGA) database and University of California Santa Cruz (UCSC) Xena, respectively. A prognostic-related feature and risk model was developed using the least absolute shrinkage and selection operator (LASSO). Subtypes were classified with consensus cluster analysis and validated with t-Distributed Stochastic Neighbor Embedding (tSNE). Kaplan-Meier analysis was conducted to assess differences in survival. Infiltration by immune cells was estimated by single sample gene set enrichment analysis (ssGSEA), Tumor IMmune Estimation Resource (TIMER) algorithm. Quantitative polymerase chain reaction (qPCR) was used to detect lncRNAs expression in clinical samples and cell lines. A series of studies was conducted in vitro and in vivo to examine the effects of knockdown or overexpression of lncRNAs on ICD. Results: In total, 16 ICD-related lncRNAs with prognostic values were identified. Using SCARNA9, FAM198B-AS1, FKBP14-AS1, FBXO30-DT, LINC01943, and AL161431.1 as risk model, their predictive accuracy and discrimination were assessed. We divided EC patients into high-risk and low-risk groups. The analysis showed that the risk model was an independent prognostic factor. The prognosis of the high- and low-risk groups was different, and the overall survival (OS) of the high-risk group was lower. The low-risk group had higher immune cell infiltration and immune scores. Consensus clustering analysis divided the samples into four subtypes, of which cluster 4 had higher immune cell infiltration and immune scores. Conclusions: A prognostic signature composed of six ICD related-lncRNAs in EC was established, and a risk model based on this signature can be used to predict the prognosis of patients with EC.

Investigation of prognostic values of immune infiltration and LGMN expression in the microenvironment of osteosarcoma.

BACKGROUND: Osteosarcoma (OS), the most common primary malignant bone tumor, predominantly affects children and young adults and is characterized by high invasiveness and poor prognosis. Despite therapeutic advancements, the survival rate remains suboptimal, indicating an urgent need for novel biomarkers and therapeutic targets. This study aimed to investigate the prognostic significance of LGMN expression and immune cell infiltration in the tumor microenvironment of OS. METHODS: We performed an integrative bioinformatics analysis utilizing the GEO and TARGET-OS databases to identify differentially expressed genes (DEGs) associated with LGMN in OS. We conducted Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to explore the biological pathways and functions. Additionally, we constructed protein-protein interaction (PPI) networks, a competing endogenous RNA (ceRNA) network, and applied the CIBERSORT algorithm to quantify immune cell infiltration. The diagnostic and prognostic values of LGMN were evaluated using the area under the receiver operating characteristic (ROC) curve and Cox regression analysis. Furthermore, we employed Consensus Clustering Analysis to explore the heterogeneity within OS samples based on LGMN expression. RESULTS: The analysis revealed significant upregulation of LGMN in OS tissues. DEGs were enriched in immune response and antigen processing pathways, suggesting LGMN's role in immune modulation within the TME. The PPI and ceRNA network analyses provided insights into the regulatory mechanisms involving LGMN. Immune cell infiltration analysis indicated a correlation between high LGMN expression and increased abundance of M2 macrophages, implicating an immunosuppressive role. The diagnostic AUC for LGMN was 0.799, demonstrating its potential as a diagnostic biomarker. High LGMN expression correlated with reduced overall survival (OS) and progression-free survival (PFS). Importantly, Consensus Clustering Analysis identified two distinct subtypes of OS, highlighting the heterogeneity and potential for personalized medicine approaches. CONCLUSIONS: Our study underscores the prognostic value of LGMN in osteosarcoma and its potential as a therapeutic target. The identification of LGMN-associated immune cell subsets and the discovery of distinct OS subtypes through Consensus Clustering Analysis provide new avenues for understanding the immunosuppressive TME of OS and may aid in the development of personalized treatment strategies. Further validation in larger cohorts is warranted to confirm these findings.